Main Conference Day 3Thursday, 12 June 2025 - European Time GMT+1

This presentation highlights the development of ARGX-117, a recycling anti-C2 antibody designed to inhibit complement activation. We trace its journey from laboratory innovation to phase 2 proof-of-concept studies, showcasing its potential as a therapeutic strategy for multifocal motor neuropathy patients.

To date, over 150 drugs have been approved by the FDA for treating or preventing autoimmune and inflammatory diseases such as rheumatoid arthritis, Crohn’s disease, and ulcerative colitis. Despite this comprehensive arsenal of therapies, there remains a significant unmet medical need for many patient groups. Elasmogen has designed a first-in-class soloMER drug conjugate tailor-made for autoimmune and inflammatory diseases. This innovative treatment utilizes a super-potent, novel-acting multivalent anti-TNFα soloMER to site-deliver an anti-inflammatory JAK inhibitor payload, Tofacitinib.

Immunocore has developed ImmTAAI, a new class of bispecific protein therapeutic designed to deliver targeted immunomodulation to treat autoimmune diseases. The effector domain comprises an agonistic anti-PD-1 VHH, which is biologically active only when target-bound and does not compete with natural ligand (PD-L1/L2), providing a wide therapeutic index. Using this targeted approach we have developed a novel bispecific molecule which specifically targets pancreatic beta cells to potentially treat type 1 diabetes.

The central role of FcRn in regulating IgG persistence and transport provides opportunities for therapy. In particular, the depletion of IgG using FcRn antagonists represents a new class of therapeutics to treat antibody-mediated autoimmunity. Recent developments related to the modulation of IgG levels, including mechanistic aspects of FcRn antagonism, will be presented.

Barzolvolimab is a first-in-class anti-KIT monoclonal antibody designed to inhibit activation of and deplete mast cells (MC) through an allosteric mechanism. Barzolvolimab contains Fc-modifications resulting in decreased FcyR binding and enhanced pharmacokinetics. Here we describe its discovery through Phase 2 clinical development and highlight its use in patients with MC-driven disorders.

SAIL66, a next-generation tri-specific T-cell engager targeting CLDN6, CD3, and CD137, was developed using proprietary Dual-Ig® technology. Dual-Ig® enables unique ability to CD3 and CD137, but not simultaneously. SAIL66 demonstrates remarkable selectivity, avoiding cross-reactivity with related CLDN family. In vitro and in vivo studies reveal SAIL66's superior T cell activation and enhanced anti-tumor efficacy compared to conventional TCEs.

T cell-engaging (TCE) multispecific antibodies demonstrate great clinical efficacy, though their molecular complexity is a challenge for drug manufacturability, developability, and obtaining desirable PK/PD properties. Here, we showcase the discovery and engineering of novel anti-CD3 heavy chain-only antibodies (HCAbs), which demonstrate T cell cytotoxicity comparable to clinically validated TCEs when paired with IgG or TCR modalities. This work introduces a flexible new tool for enabling this important class of biologics.

Bispecifics and multispecifics that use only one light chain are a preferred format in view of manufacturability. We have established straightforward procedures to generate common light chain multispecifics from existing monospecific therapeutic antibodies, and we have also implemented an approach to obtain 2-in-1 symmetric antibodies where the light and heavy chain bind to different targets. We demonstrate that for bispecific multivalent T cell engagers the placement geometry of the binding modules is pivotal in controlling potency and mitigating cytokine release.