Main Conference Day 2Tuesday, 15 December 2026 - PT (Pacific Time, GMT-08:00)

Electron Density Topography (EDT) is a solution-based imaging technology under development by Rigaku that enables overnight low-resolution epitope mapping directly from X-ray scattering data. We present practical workflows validated using GST–VHH complexes and extended to intact IgG–antigen complexes. EDT delivers rapid structural feedback compatible with iterative therapeutic antibody engineering while complementing established high-resolution structural methods.

How T cells integrate signals from multiple receptors is poorly understood. We will show that sub-micrometre microvillar “close contacts” formed by T cells interacting with their targets are sites of early signal integration, using the T-cell receptor and PD-1 as exemplars. A PD-1 blocking antibody induced inhibitory signaling when Fc receptor engagement enhanced PD-1 trapping at these contacts. Engineering the antibody to avoid trapping eliminated this effect, improving blockade efficacy.

CD19 is the primary amplifying co-receptor on B cells and is an important target for antibody-based therapeutics for the treatment of B cell malignancies and autoimmune disorders. Here, we report the engineering and characterization of two novel anti-CD19 clones with novel epitopes and functional properties to modulate B cell signaling.

I will present SureTAC™, a novel platform that selectively degrades disease-driving membrane proteins via the endo-lysosomal pathway. Unlike conventional blockers, SureTACs offer deeper inhibition and access to previously undruggable targets. Using PD-L1 proof-of-concept data in vitro and in vivo, I will highlight the therapeutic potential across oncology and inflammation to advance first-in-class therapies for improved patient outcomes.

Current ADCs face limitations from poor target internalization and healthy tissue expression. Tacalyx addresses this by developing antibodies against tumor-associated carbohydrate antigens (TACAs). Because TACAs are densely displayed across most cell-surface proteins, their engagement triggers rapid, robust crosslinking and internalization via multiple endocytic pathways, driving highly efficient cell killing and potentially mitigating payload resistance. Preclinical data demonstrate this platform’s strong therapeutic efficacy. The lead candidate is undergoing CMC development ahead of Phase I trials next year.

This presentation will highlight E-688/HLX316, a sialidase-armed anti-B7-H3 nanobody that leverages targeting-induced proximity to drive deep and sustained tumor desialylation. E-688 achieved >1,000-fold enhanced desialylation potency and robust single-agent antitumor activity across multiple mouse models, with a favorable safety profile in NHPs, demonstrating the potential of targeted desialylation as a new immuno-oncology approach.

High-throughput antibody discovery can identify more hits than teams can efficiently express, purify, and functionally evaluate. This presentation explores how integrating Pfenex into existing screening workflows could provide earlier expression, quality, and developability insight for antibody fragments without replacing established discovery infrastructure. Attendees will learn how expression of hits in Pfenex improves throughput, material availability, and accelerates lead candidate selection.

Antibody discovery driven by AI generates thousands of candidates, but validation via mammalian expression remains slow. We present an engineered cell-free protein synthesis (CFPS) workflow that inserts a rapid triage step before scale-up. By delivering decision-grade kinetics directly from cell-free material, this platform enables confident early go/no-go decisions and protects downstream capacity—the missing upstream triage step in modern antibody hit validation.

PUREfrex® is a fully reconstituted, cell free protein expression system enabling rapid, high throughput antibody engineering. It efficiently produces scFv, Fab, and IgG, and supports robust ribosome display (PUREfrexRD) for screening highly diverse libraries. Combined with AI/ML workflows, PUREfrex® accelerates discovery of next generation antibodies and cyclic peptide modalities with enhanced precision, flexibility, and scalability for biologics R&D.

Amyotrophic lateral sclerosis (ALS) is characterized by motor neuron degeneration and pathological TDP-43 mislocalization, aggregation, and loss of nuclear function. We developed an AAV-delivered ScFv that selectively targets cytoplasmic TDP-43 while preserving native protein. By binding the C-terminal domain, it restores nuclear function, reduces aggregates, and improves protein homeostasis. Preclinical studies and biodistribution data demonstrate therapeutic potential, supporting further clinical development as a disease-modifying treatment for ALS and other TDP-43 proteinopathies.

The inability of antibodies to penetrate the blood–brain barrier is a major limitation to their use in CNS therapeutics. We developed dual-targeting bispecific antibodies that engage the transferrin receptor and a neuronal cell-surface protein, enabling increased CNS accumulation and enhanced neuronal localization. Conjugation of antisense oligonucleotides to these bispecific antibody shuttles enabled efficient gene silencing across multiple CNS regions and neuron-specific gene modulation.

Neutralization of genetically diverse viruses can be enhanced by molecules that combine multiple copies of antibodies with various specificities. Here, we discuss the neutralization resilience of such molecules against HIV, as well as pharmacokinetics considerations in higher-order model species to translate IgG-like exposure into broad viral neutralization at low concentrations.

Progressive fibrosis is a key driver of chronic disease progression, with limited therapeutic options. Although TGF-β1 blockade shows potential, safety and pharmacokinetic challenges have hindered clinical development. We developed a pH-dependent anti-latent TGF-β1 recycling antibody to overcome target-mediated clearance. The anti-latent TGF-β1 recycling antibody demonstrated prolonged exposure in cynomolgus monkey and suppressed fibrosis in multiple mouse models, supporting latent TGF-β1 targeting with recycling antibody technology as a promising therapeutic strategy for fibrosis-related indications.

Protein misfolding diseases demand antibodies that selectively target scarce, pathological protein conformations while sparing abundant native forms. Paradox Immunotherapeutics employs a validated, structure-based approach to predict misfolding-specific epitopes, enabling precise clearance of disease-causing proteins. Modality-agnostic in discovery, we're eager to explore partnerships advancing high-value targets in systemic amyloidosis and beyond.