RGX-019-MMAE

RGX-019-MMAE is a novel antibody-drug conjugate (ADC) targeting MERTK (c-Mer proto-oncogene tyrosine kinase), a member of the TAM receptor tyrosine kinase family. Developed by Inspirna, the drug consists of a humanized IgG1 monoclonal antibody (RGX-019) conjugated to the microtubule-disrupting agent monomethyl auristatin E (MMAE). MERTK is overexpressed in various solid and hematologic malignancies, where it promotes tumor cell survival and immunosuppression. RGX-019-MMAE binds to MERTK with high affinity, triggers receptor internalization, and releases MMAE to induce cytotoxicity in actively dividing cancer cells. It also exhibits a bystander effect, allowing it to kill neighboring MERTK-negative cells. Preclinical studies have demonstrated efficacy in triple-negative breast cancer (TNBC), acute myeloid leukemia (AML), and multiple myeloma (MM), while sparing non-dividing cells like retinal pigment epithelium to avoid toxicities associated with MERTK inhibition.