AMHR2 and GM102

AMHR2 program

The anti-AMHR2 mAb, GM102 (formerly 3C23K) is an Emabling engineered humanized mAb directed against the receptor of the anti-Müllerian hormone (AMHR2), alternatively known as Müllerian Inhibiting Substance Receptor II (MISRII). AMHR2 is present during intra-uterine period at the level of internal sexual female organ precursors (Müllerian tractus), and is restricted to ovary (Granulosa cells) and testis (Leydig cells) during adulthood. Several authors have shown by immuno-chemistry using the antibody 12G4 (the murine precursor of GM102 discovered at Institut de Recherche en Cancérologie de Montpellier) that AMHR2 is also expressed in the majority of gynecologic cancers such as ovary and endometrium (Bakkum JN, Gynecol Oncol, 2007; Sahli I, Biochem, 2004; Anttonen M, Lab Invest, 2011; Song JY, Int J. Oncol, 2009) with an incidence of around 65% of the cases.

Through a solid research dossier of about twenty in vivo studies exploring various doses, schemes of administration and treatment combinations, the GM102 antibody has been shown to display a high efficacy in relevant mice xenografted models, including Patient Derived Xenografts models expressing human AMHR2. This efficacy has been documented to rely on engagement of immune effector cells triggered by the Emabling optimized antibody at the level of the tumor. In addition, GM102 efficacy has been shown to be synergistic with carboplatin and paclitaxel, the major chemotherapeutic agents used in ovarian cancer (Jacquet A, Cancer Res, 2012).

GM102 program

The GM102 mAb has started a Phase Ia/Ib study in advanced, pre-treated gynecological cancers (ovarian, endometrium, cervix).

The primary objective is to assess the safety of GM102, select a dose for future Phase Ib/II trials and provide early evidence of therapeutic efficacy of GM102  in subsets of patients.