Main Conference Day 3 - 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.
DuoBody®-EpCAMx4-1BB (BNT314/GEN1059) is an investigational Fc-silenced bispecific antibody (bsAb) designed to boost antitumor immune responses through EpCAM-dependent 4-1BB agonist activity. EpCAMx4-1BB bispecific enhanced T cell proliferation, activation and cytotoxic capacity of activated T cells in vitro and exhibited antitumor activity in vivo. Moreover, combining EpCAMx4-1BB with PD-1/PD-L1 axis blockade potentiated all these responses. These data provide preclinical rationale for the clinical evaluation of DuoBody-EpCAMx4-1BB.
Stellabody® is a single point mutation in the CH3 region that facilitates “on-target assembly” of immune biologics that transforms killing or agonistic potency in multiple immune protein formats i.e. mAbs, bispecific antibodies, Fc-fusions and novel scaffolds. Stellabody biologics mediate greatly (10-100x) enhanced potency in head-to-head comparisons with the equivalent standard biologic including standard-of-care mAbs in oncology on primary patient-derived clinical samples and targets in infection and immunology.
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.
Multivalent interactions enable complex molecular recognition and signaling processes, such as the initiation of the classical complement pathway (CCP). This presentation gives an overview on how the CCP is initiated through antigen-dependent oligomerization of IgGs and subsequent recognition and activation of the multivalent zymogen C1. The presented kinetic model may serve as a basis for optimizing antibody-engineering and PK/PD modelling.
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.