Johnson & Johnson announced the planned presentation of new non-clinical studies underscoring the molecular properties of nipocalimab, an investigational fully human monoclonal antibody targeting the neonatal fragment crystallizable receptor (FcRn). These data showcase the promise of nipocalimab as a potential best-in-class FcRn blocker and unique characteristics including its high binding affinity and specificity to the immunoglobulin G (IgG) binding site of FcRn. These properties, along with the dosing regimen chosen for study contribute to its dose- and time-dependent receptor occupancy, resulting in the rapid, deep and sustained lowering of IgG, including IgG autoantibodies in neuroimmune diseases such as generalized myasthenia gravis (gMG) and other autoantibody-driven diseases.

The data will be one of six scientific posters the Company will present at the American Academy of Neurology's (AAN) 2024 Annual Meeting (Poster 14-008). gMG is a highly debilitating, rare autoantibody-driven disease for which there currently is no cure, characterized by fluctuating weakness of the skeletal muscles leading to symptoms like difficulty speaking and allowing. A Phase 2 clinical study with nipocalimab published in Neurology (2024) demonstrated MG patients with a greater magnitude of IgG lowering tended to have greater improvements in key efficacy outcomes (e.g., MG-ADLa).

Nipocalimab is the only FcRn blocker being studied across three key segments of auto- and alloantibody driven diseases, including Maternal Fetal, Rare Autoantibody and Prevalent Rheumatology.1 Within the past year nipocalimab has demonstrated clinical effect in four autoantibody-driven diseases across all three segments: hemolytic disease of the fetus and newborn in Maternal Fetal, gMG in Rare Autoantibody, and Sjögren's disease and rheumatoid arthritis in Prevalent Rheumatology. Nipocalimab exhibits non-pH-dependent, high binding affinity, enabling it to decrease maternal circulating IgG levels and block maternal to fetal IgG transfer with minimal evidence of transplacental transfer to the fetus. These properties contribute to the position of nipocalimab as the only FcRn blocker being studied in maternal fetal indications. Not only are these indications of high unmet medical need, but generating data in pregnancy is differentiating because approximately 80% of patients living with autoantibody-driven diseases are female, and up to half are of childbearing potential. Nipocalimab was granted Fast Track designation in HDFN and warm autoimmune hemolytic anemia (wAIHA) in July 2019, gMG in December 2021 and fetal neonatal alloimmune thrombocytopenia (FNAIT) in March 2024 and was granted orphan drug status for wAIHA in December 2019, HDFN in June 2020, gMG in February 2021, chronic inflammatory demyelinating polyneuropathy (CIDP) in October 2021 and FNAIT in December 2023 by the U.S. Food and Drug Administration (FDA).

The investigational treatment for HDFN was also granted Breakthrough Therapy Designation by the FDA in February 2024, and orphan medicinal product designation by the European Medicines Agency in October 2019. Myasthenia gravis (MG) is an autoantibody disease where autoantibodies target proteins at the neuromuscular junction, disrupt neuromuscular signaling, and impair or prevent muscle contraction.5 The disease impacts an estimated 700,000 people worldwide, with 85% of these patients experiencing the more extensive form of the disease, gMG.5 In MG, the immune system mistakenly attacks muscle receptors by producing anti-receptor antibodies (e.g.,anti-acetylcholine receptor [AChR], anti-muscle-specific kinase [MuSK] or anti-low density lipoprotein-related protein 4 [LRP4]) that can block or destroy these muscle receptors, preventing signals from transferring from nerves to muscles.6 Symptoms include limb weakness, drooping eyelids, double vision, and difficulties with chewing, swallowing, speech, and breathing. Although gMG may be managed with current therapies, research is needed to develop new treatments for those who may not respond well enough to or tolerate current therapies.

Nipocalimab is an investigational, high-affinity, fully human, aglycosylated, effectorless, monoclonal antibody that aims to selectively block FcRn to reduce levels of circulating immunoglobulin G (IgG antibodies, including autoantibodies and alloantibodies that underlie multiple conditions. Nipocalimab is the only FcRn blocker being studied across three key segments in the autoantibody space: Rare Autoantibody diseases (e.g., generalized myasthenia gravis in adults and children, chronic inflammatory demyelinating polyneuropathy, warm autoimmune hemolytic anemia, and idiopathic inflammatory myopathies); Maternal Fetal diseases mediated by maternal alloantibodies (e.g., hemolytic disease of the fetus and newborn and fetal and neonatal alloimmune thrombocytopenia); and Prevalent Rheumatology (e.g., rheumatoid arthritis, Sjögren's disease, and systemic lupus erythematosus). Blockade of FcRn has the potential to reduce overall IgG including pathogenic alloantibody levels while preserving immune function without causing broad immunosuppression.

Blockade of IgG binding to FcRn in the placenta is also believed to prevent transplacental transfer of maternal alloantibodies to the fetus.