Characterization of MEN1309/OBT076, a new antibody conjugated to the DM4 maytansinoide toxin

CD205 is a type I transmembrane glycoprotein, member of C-type lectin receptor family. Analysis by mass spectrometry revealed that CD205 antigen was robustly expressed and highly prevalent in a variety of solid malignancies of different histotypes. Immunohistochemistry (IHC) confirmed the increased expression of CD205 antigen in pancreatic, bladder and triple negative breast cancer (TNBC) malignancies compared to corresponding normal tissues. Using immunofluorescence microscopy, rapid internalization of the CD205 antigen was observed. These results supported the development of MEN1309/OBT076, a fully human CD205-targeting monoclonal antibody conjugated to DM4, a potent maytansinoid derivate, via a cleavable N-succinimidyl-4-(2-pyridyldithio) butanoate linker. MEN1309/OBT076 was characterized in vitro for target binding affinity, mechanism of action (MoA) and cytotoxic activity against a panel of cancer cell lines demonstrating selective and potent cytotoxic effects against tumor cells with strong and low to moderate CD205 antigen expression. In addition, MEN1309/OBT076 showed potent antitumor activity resulting in durable responses and complete tumor regressions in many xenografts of TNBC, pancreatic, bladder cancer cell-lines as well as in patient-derived xenograft (PDX) models. Finally, the pharmacokinetics (PK) and pharmacodynamics (PD) profile of MEN1309/OBT076 was characterized in a mouse model harboring a pancreatic tumor. Overall, these data demonstrate that MEN1309/OBT076 is a novel and selective antibody-drug conjugate (ADC) with potent activity against CD205 antigen positive tumors. These data supported the clinical development of MEN1309/OBT076 in the phase I of “SHUTTLE” clinical trial, currently ongoing.