Main Conference Day 1Monday, 15 December 2025 - PT (Pacific Time, GMT-08:00)

The cell surface proteome, the surfaceome, is the major hub for cellular communication and a primary source of drug targets. We have been developing new proteomic approaches to probe the surfaceome for novel cancer-associated changes in expression, proteolysis, glycosylation, immunopeptidomes, and complexes. This has lead us to build new TCE’s, ADC’s, and extracellular targeted degraders (eTPD) to better attack the cancer surfaceome.

Inhibitory receptor agonism is important for maintaining normal immune homeostasis in healthy individuals. Agonizing inhibitory receptors with antibodies offers a differentiated approach for treating the uncontrolled inflammatory responses observed in autoimmune disease. Understanding and mimicking the biology of natural receptor and ligand interactions is critical for designing therapeutics with optimal inhibitory receptor agonism, and can differ from traditional therapeutic antibody discovery approaches.

The measles vaccine is a global success story, yet what human antibodies are elicited by this vaccine and their structures remain unknown. We generated a large panel of human mAbs from a vaccine, mapped epitopes biochemically and by cryoEM and found potent neutralization and in vitro protection via complementary mechanisms. mAbs against both the attachment antigen H and fusion antigen F are protective and offer therapeutic cocktails for treatment or prevention.

Over the past century, our industry progressed from identifying natural products with favorable pharmacology mediated by unknown molecular mechanisms, to deliberate engineering of biologics that engage prespecified targets and alter their activities in predefined ways. The past two decades have seen the emergence of an entirely new category – multispecifics – that engage two or more targets. This elicits emergent properties that enable biologics to circumvent natural barriers to pharmacology, including rapid clearance, functional redundancy, on target/off-tissue toxicity, and lack of druggable features. I will discuss how multispecifics are recalibrating expectations of what can be achieved through pharmacotherapy.

OptiMAL™ represents the World's first platform using a fully synthetic human antibody library that can be screened using Mammalian Display in the native IgG format. The results shown will demonstrate that this platform can be used for the discovery of antibodies with high specificity, developability and yield, in a competitive timeframe. Followed by the knowledge that a rationally designed synthetic library can out-perform more traditional library design methods.

This topic explores the revolutionary potential of the genome-edited mouse, where endogenous VH and VL genes are replaced by fully human VH and VL genes in situ, enabling the generation of fully human antibody molecules. When combined with Biointron's AbDrop microfluidic technology-enhanced single B cell screening, this approach allows for the high-throughput and efficient discovery of antibody drug molecules.

Dr. Barry Duplantis has a strong technical background and over a decade of experience applying drug and vaccine discovery and development platforms in commercial settings. He was the founder and CEO of a biotech startup and later led client relations at a global contract research organization. Dr. Duplantis earned his Ph.D. in Biochemistry and Microbiology from the University of Victoria, where his research focused on intracellular pathogenesis.

The antibody molecule is a wonder of nature that connects disease targets with immune effector cells via its Y-shaped topology of three domains connected by a hinge region. We describe GEM-DIMER technology allowing us to create superdimers of two antibodies interconnected at their hinge regions by a strong non-covalent interaction. Our superdimers demonstrate cooperative binding to disease targets and immune effector cell receptors, making them ideal for human therapeutic applications.

Antibodies have broad utility in imaging, targeted gene delivery, and disease therapy, and many of these applications require conjugation to secondary molecules. Unfortunately, conventional conjugation approaches are limited by destabilization of structure, heterogeneity, and technically demanding multi-step reactions. To overcome these challenges, we developed a straightforward and highly general platform for site-specific antibody conjugation that blends metabolic glycoengineering with protein design, presenting a highly efficient strategy to produce antibody conjugates.

Antibodies targeting human cytomegalovirus (CMV) exhibit limited efficacy due to immune evasion mechanisms, including viral receptors that capture human Fc domains. We engineered Fc variants that retain binding to host receptors but exhibit markedly reduced binding to viral Fc receptors. Antibodies with engineered Fc domains mediated enhanced CD16A activation and limited viral spread in CMV-infected fibroblasts more effectively than wild-type Fc.

The efficiency of complement activation among IgG subclasses is primarily determined by their capacity to form oligomers upon binding to antigens. This oligomerization facilitates the multivalent engagement of the C1 complex, thereby initiating the classical complement pathway. These insights offer a mechanistic understanding that could inform the design of antibody therapies with enhanced effector functions.