Abstract Details

Title Nipocalimab’s Selective Targeting of FcRn and IgG Clearance Preserves Key Immune Functions

Topic Autoimmune Neurology

Presentation(s) P1 - Poster Session 1 (9:00 AM-5:00 PM)

Poster/Presentation
Number 010

Objective

To characterize the effect of nipocalimab, a fully human, effectorless IgG1 anti-neonatal Fc receptor (FcRn) monoclonal antibody on immune function.

Background Nipocalimab binds to FcRn with high affinity which prevents IgG recycling, leading to reduced serum levels of total IgGs, including pathogenic IgG autoantibodies. Rapid, sustained lowering of IgG was observed in the phase 2 VIVACITY study in generalized myasthenia gravis (gMG) and in phase 1 healthy volunteers. In gMG patients, nipocalimab induced rapid and sustained lowering of anti-AChR autoantibodies and MG-ADL scores, but no serious adverse events including clinically significant infections.

Design/Methods Nipocalimab was evaluated extensively in vitro and in nonhuman primate-based chronic toxicology studies to evaluate selectivity, tolerability, safety and immunopharmacology. Safety, tolerability and immune-focused assessments in clinical phase 1 and Phase 2 MG studies were also completed (NCT02828046, NCT03772587).

Results Nipocalimab binds specifically in vitro to FcRn without activation of effector function or inhibition of antigen presentation. In nonhuman primates administered up to 300 mg/kg nipocalimab QW for up to 6 months, sustained lowering of IgG was observed without adverse effects. Immunotoxicology identified no effect on immune cell phenotypes; CD8 T cell, NK or innate cell functions; T-dependent neoantigen IgM responses. Neoantigen IgG production was observed, but with lowered peak IgG titers consistent with the anticipated increase in IgG clearance with nipocalimab. In clinical studies, nipocalimab demonstrated a reproducible selective decrease in total serum IgG, including all subclasses of IgG, with no effect on IgM, IgA, IgE, CH50, C3, C4, inflammatory cytokines or acute phase proteins including, C-reactive protein (CRP).

Conclusions These data suggest that nipocalimab can selectively lower IgG and IgG autoantibodies while preserving cellular immunity, complete IgM response and IgG production after neoantigen challenge. Overall, nipocalimab’s selective effect on IgG recycling provides a mechanistic rationale for potentially decreased infection risk despite substantial IgG lowering.

Authors/Disclosures
Judith Profant PRESENTER	Judith Profant has received personal compensation for serving as an employee of Janssen Pharmaceuticals .
Leona Ling, PhD (Janssen Pharmaceuticals (J&J))	Dr. Ling has received personal compensation for serving as an employee of Janssen Pharmaceuticals (Johnson&Johnson). Dr. Ling has stock in Janssen Pharmaceuticals (Johnson&Johnson). Dr. Ling has received intellectual property interests from a discovery or technology relating to health care. Dr. Ling has received intellectual property interests from a discovery or technology relating to health care.
Steven Tyler (AVROBIO Inc)	No disclosure on file
	No disclosure on file
	No disclosure on file
Julia Brown (Janssen Pharmaceuticals)	No disclosure on file
	No disclosure on file
Rui Xu (Janssen Pharmaceutical)	No disclosure on file
	No disclosure on file
William Avery (Kisbee Therapeutics)	William Avery has stock in Nuvig Therapeutics.

��ɫ��

��ɫ��