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Background
MGC026 is an investigational, clinical ADC incorporating a B7-H3-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. The variable domain of the molecule targeting B7-H3 is the same sequence contained in vobra duo.
We view MGC026 as a complementary approach to vobra duo for targeting B7-H3. More specifically, we believe that having distinct mechanisms of action, vobra duo and MGC026 may address different cancers, tumor stages, or be used in combination with alternate agents or potentially with one another to enhance their clinical utility. We remain confident in the potential of targeting the B7-H3 pathway, viewing our TOP1 inhibitor strategy as an additional, valuable tool in our therapeutic repertoire.
Clinical Development
Please refer to our most recent corporate deck on our Events & Presentations page for the latest clinical information available on MGC026.
Our Rights
MacroGenics retains global rights to MGC026.
Clinical Trials
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.