Main Conference Day 1Tuesday, 10 June 2025 - BST (British Summer Time, GMT+1)

The cytosolic Fc receptor TRIM21 uses antibodies to target proteins for degradation inside the cell. This activity provides potent immune protection by destroying incoming viral particles and underpins “Trim-Away” technology. In my talk I will discuss our recent work on the molecular mechanism of cytosolic antibody-mediated degradation and the use of Trim-Away degraders to remove tau aggregates in vivo in a mouse model of Alzheimer’s Disease.

This presentation highlights efforts to develop novel transport vehicle (TV) enabled antibodies for AD that target microglia function. We’ve developed distinct transport vehicle platforms that can be differentially applied to antibodies to increase brain exposure, improve biodistribution, and enhance activity of Fab-mediated target engagement.

Tau is inextricably linked to a group of clinically diverse neurodegenerative diseases termed tauopathies. The ratio balance of the major tau splicing isoform groups (3R- and 4R-tau) is critical in maintaining healthy neurons. An imbalance causing excess 4 R tau is associated with diseases such as progressive supranuclear palsy. The work presented in this talk covers the generation of a novel 4R-tau specific “degrabody” capable of degrading 4R tau in iPSC derived neurons to probe its potential role in neurodegeneration.

The tumor microenvironment is complex, frequently immune suppressive and has become established as a critical determinant of response to antibody therapy. Understanding the tumor microenvironment in patients, including the contribution of host factors such as body composition and metabolic dysregulation on its inflammatory status, and modelling these effectively will likely be critical to advancing drug development and combination strategies. Here we will present data demonstrating that metabolic modifiers can alter the tumour immune environment in patients and then using preclinical models that this can be used in combination therapy to enhance response to immune checkpoint blockade.