Endpoints: Critical Preclinical Markers in Extracellular Protein Degradation Assays

Therapeutics that leverage protein degradation as their primary mechanism of action appear to be a validated new therapeutic modality. The current clinical molecules are focused on degrading intracellular targets. Extracellular targeted protein degradation (eTPD) has emerged as a promising new drug modality focused on targeted elimination of pathogenic extracellular and transmembrane proteins. In contrast to intracellular protein degraders, which require ubiquitin-proteosome cellular degradation, extracellular protein degraders can also harness endosomal-lysosomal protein degradation pathways.

EpiTACs are an example of an extracellular protein degradation therapeutic. These are tissue-specific bispecific antibodies in which one arm binds a target and the other arm binds a degrader receptor. EpiTACs leverage a novel atlas of tissue-enriched degrader receptors comprised of transmembrane ligases, cytokine/chemokine receptors, and internalizing receptors resulting in selective degradation of membrane and soluble proteins.

In this GEN webinar, Shyra Gardai, PhD, will demonstrate the potential of this novel extracellular degrading platform using the development of bispecific antibodies to degrade the canonical receptor tyrosine kinase epidermal growth factor receptor (EGFR) as a case study. She will share data that demonstrates EpiTACs’ potential to overcome the limitations of current therapeutic modalities using cell-based assays that evaluate critical markers, including EGFR antagonism, internalization, and degradation. She will also share results showing robust tumor-suppressive effects of EpiTACs in tumor spheroids and xenograft mouse tumor models.

A live Q&A session followed the presentation, offering a chance to pose questions to our expert panelist.