Effects of ICOS+ T cell depletion via afucosylated monoclonal antibody MEDI-570 on pregnant cynomolgus monkeys and the developing offspring

•Inducible T-cell costimulator (ICOS) blockade may be a promising new approach for therapeutic intervention in autoimmune disease.•MEDI-570 selectively depletes ICOS-bearing T cells and was administered SC to pregnant cynomolgus monkeys throughout gestation.•Decreased populations of peripheral blood T lymphocytes were seen in dams and infants and a delayed and decreased immune response to KLH was observed in the infants.•Development of a fibromatosis mass in one dam and development of atypical lymphoid hyperplasia in 2 infants.•Women of child bearing potential should employ effective methods of contraception while being treated with MEDI-570. MEDI-570 is a fully human afucosylated monoclonal antibody (MAb) against Inducible T-cell costimulator (ICOS), highly expressed on CD4+ T follicular helper (TFH) cells. Effects of MEDI-570 were evaluated in an enhanced pre-postnatal development toxicity (ePPND) study in cynomolgus monkeys. Administration to pregnant monkeys did not cause any abortifacient effects. Changes in hematology and peripheral blood T lymphocyte subsets in maternal animals and infants and the attenuated infant IgG immune response to keyhole limpet hemocyanin (KLH) were attributed to MEDI-570 pharmacology. Adverse findings included aggressive fibromatosis in one dam and two infant losses in the high dose group with anatomic pathology findings suggestive of atypical lymphoid hyperplasia. The margin of safety relative to the no observed adverse effect level (NOAEL) for the highest planned clinical dose in the Phase 1a study was 7. This study suggests that women of child bearing potential employ effective methods of contraception while being treated with MEDI-570.