Main Conference Day 1Monday, 14 December 2026 - PT (Pacific Time, GMT-08:00)

Proteolysis-targeting antibodies (PROTABs) are bispecific molecules that recruit cell-surface E3 ubiquitin ligases to transmembrane target proteins, driving ubiquitin-mediated degradation. Through integrated biochemical, cellular, and structural analyses, we demonstrate that the geometry of target engagement is a primary determinant of both degradation efficiency and the specific mechanism of action (MOA). These mechanistic insights, combined with prior findings, provide a robust foundation for the rational design and engineering of antibody-based degraders.

Our aim is to convert any clinical antibody or protein therapeutic, all of which are injectables, into oral pill formulations. We have developed a bispecific protein therapeutic (UTAC) consisting of a human pancreatic enzyme, which retro-transcytoses from gut lumen into blood, fused to anti-IgG moieties. Co-formulating UTAC with a clinical antibody, and leveraging Intract’s core pharmacy technologies, achieves high antibody bioavailability in blood in mice after intraduodenal administration. Finally, we’ll present impressive UTAC pilot data from cynomolgus macaque.

Interleukin-12 (IL-12) is a potent immunostimulatory cytokine whose clinical utility is constrained by systemic toxicity. Here, we report a protease-activatable IL-12 masking platform integrating intramolecular VH-mediated inhibition with tumor-associated protease–triggered activation. IL-12 activity is effectively suppressed in the intact state and selectively restored upon proteolytic cleavage, with activation tunability achieved through VH interface engineering. Incorporation of a Y16P mutation further expands the activation window. In vivo, this design preserves antitumor efficacy while markedly improving tolerability, highlighting a generalizable strategy for safer cytokine therapeutics.

Understanding the biology of human antigen-specific plasma cells at a single cell level using a bone marrow mimetic organoid system. Most plasma cells die immediately after removal from the blood or tissue sites. We have developed an experimental system to maintain survival of human plasma cells to identify antigen-specificity for monoclonal antibody generation.