Main Conference Day 3Wednesday, 16 December 2026 - PT (Pacific Time, GMT-08:00)

Autoimmune and inflammatory diseases involve complex, interconnected immune pathways, making bispecific (bsAbs) and multispecific antibodies (multi-Abs) promising next-generation therapeutics. Primarily driven by oncology — accounting for 18 of 21 approved therapies — interest in applying these modalities to immune-mediated diseases is rapidly growing. Early studies suggest dual- and multi-targeting strategies may improve efficacy, selectivity, and safety. The presentation covers multispecific therapeutic strategies targeting cytokines, immune receptors, pathogenic cell populations, while highlighting future opportunities and challenges.

We report a modular platform that leverages the endocytic inhibitory receptor FcgRIIB to facilitate selective clearance of pathogenic autoantibodies while sparing the total IgG pool. This platform utilizes a triple-action mechanism: first, it neutralizes autoantibodies by binding and forming small immune complexes (ICs); second, it triggers rapid clearance of these ICs via endocytic cells through avidity-mediated engagement of FcgRIIB; and third, it inhibits pathogenic B cells selectively by co-ligating the B-cell receptor with FcgRIIB.

MPACT repurposes the native IgG Fc–FcγR interaction as a covalent docking site, using a single engineered disulfide bond to create mixed-valency, modular multispecific antibodies. The platform enables rapid addition of targeting domains, immune agonists, cytokines, and protease-activated payloads while preserving IgG-like expression and pharmacologic properties. Examples will highlight tunable avidity, antigen-selective T-cell engagement, conditional activation, and in vivo antileukemic activity.

Pathogenic immunoglobulin G (IgG) antibodies are central drivers of a wide range of antibody mediated and autoimmune disorders. Existing strategies to reduce IgG levels are often limited by inefficient IgG depletion, subclass bias, or safety concerns related to Fc mediated effector functions and FcRn biology. Here, we present an innovative antibody approach for efficient, sustained and selective IgG removal. Ig-ABDEG is a first-in-class, Fc-silenced IgG sweeping antibody designed to achieve rapid, deep, and sustained pan-subclass IgG reduction while preserving a favorable safety profile. By combining high affinity IgG capture at physiological pH with release at endosomal pH and FcRn optimized trafficking, Ig-ABDEG enables efficient lysosomal clearance of all IgG subclasses without affecting other immunoglobulins, FcRn integrity, or albumin levels. This mechanistically differentiated approach supports chronic use in IgG mediated diseases, with a first-in-human study currently ongoing.

Our group has developed a portfolio of novel Fc variants comprising distinct designs for enhanced target-cell clearance, complete silencing of Fc-mediated effector functions, extended serum persistence, and accelerated elimination of pathogenic IgG autoantibodies. Their marked functional gains relative to established Fc variants incorporated into marketed therapeutics will be presented.