In this presentation, a novel peptide linker technology for site-specific payload conjugation will be introduced that enables the generation of antibody-drug conjugates (ADCs) directly from native antibodies off the shelf in one step, without the need of any upfront antibody engineering. The resulting ADCs show remarkable in-vivo stability and antibody-like PK exposure with excellent activity at low doses and high tolerability in rats and monkeys. Using this novel linker technology, a low drug-load ADC carrying a topoisomerase-1 inhibitor was generated showing significant and efficient tumor growth inhibition head-to-head vs. trastuzumab deruxtecan. These data highlight the potential of this innovative peptide linker technology in enhancing the therapeutic efficacy and tolerability of ADCs.

Fcab-Drug Conjugates are a novel ADC format carrying an Fc antigen binding fragment (Fcab) as targeting scaffold instead of an IgG antibody. The combination of Fcabs’ small size, antigen binding capabilities, and relatively long half-life makes them a promising scaffold for the generation of drug conjugates with improved tissue penetration capabilities compared to classical IgG-based ADCs. This talk covers the concept and format exploration data.

C'Dot Drug Conjugates (CDCs) are targeted ultra-small (~6nm diameter) nanoparticles composed of a silica core and a layer of short PEG chains conjugated to high concentrations of payload and targeting moieties. Elucida's preclinical work developing novel exatecan-conjugated, anti-tissue factor (CD142) VHH single domain antibody-targeted CDCs that are capable of delivering high concentrations of payload, penetrating deep into tumors and avoiding healthy tissue will be presented.

This presentation will discuss the preclinical efficacy and safety of BYON3521 and share updates from clinical phase 1A trials.

Intracellular antibodies are a starting point as inhibitors via design to block protein-protein interactions or to carry effector functions. Expressing fusions of intracellular antibodies with E3 ligase creates biodegraders to eliminate target proteins, or with procaspases to cause antigen-dependent cell death. The targeting LMO2 and mutant RAS is POC for intracellular antibodies as drugs per se.

Antibody therapy based on glycan targets remains attractive. We will present preclinical results from reformatting these antibodies to T cell redirecting bispecifics, ADC, as well as their potential for CAR therapy; showcasing their versatility. Combination therapy may be warranted for optimising their efficacy towards solid tumours. 

We have developed mutually-dependent IgG antibody combinations engineered to selectively act on cells co-expressing two antigens. Genmab’s HexElect technology is based on Fc-domain engineered IgG antibody pairs that act as Bio-Logic AND gates selectively activated after hetero-oligomerization. Functional activation of complement or signaling by HexElect antibody pairs was stringently dependent on the presence of two targets co-expressed at the same cell surface. HexElect technology may enable access to an untapped, combinatorial target space for the generation of antibody therapeutics that exhibit both selectivity and potency.

SNS-101 is a conditionally active anti-VISTA antibody designed to relieve T cell suppression driven by the VISTA-PSGL-1 immune checkpoint within the acidic tumor-microenvironment, currently in a Phase I study. SNS-101 displayed strong anti-tumor activity in syngeneic tumor models as both monotherapy and in combination with PD-1 blockade. pH-selective target engagement resulted in a significantly improved safety and pharmacokinetic profile in non-human primates, suggesting SNS-101 may overcome prior hurdles of anti-VISTA biologics. 

STA551 is a clinically investigated anti-CD137 agonist antibody that activates immune cells only in the presence of extracellular ATP. Previous study showed a synergistic efficacy of combining STA551 with anti-PD-L1 antibody. Using scRNA-seq, I tried to elucidate the mechanism and found this effect was due to an increase in activated T cells and a decrease in exhausted T cells. I would like to discuss the detail mechanism of action of STA551.

Local immunotherapy is attractive to overcome the challenges of off-tissue toxicity and limited bioavailability observed with systemic delivery of immunotherapies. Here, we demonstrate that we can enhance intratumoral retention and reduce undesired systemic circulation of immune checkpoint inhibitor antibodies in tumors using cationic peptides as safe anchors to the tumor microenvironment.