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Protein Homeostasis

BPGbio’s Protein Homeostasis program is built around a First-In-Class ubiquitin conjugating enzyme (E2) based targeted protein degradation (TPD) platform (“E2 Platform”).

Drugging the Undruggable

TPD has gained momentum in recent years as a strategy for modulating difficult-to-target proteins or protein targets that do not offer beneficial clinical outcomes from traditional small molecule inhibition. Conventional degraders utilize E3 enzymes to achieve degradation. E2 enzymes were recently demonstrated by Poirson et al to be potent effectors of TPD.

The E2 Advantage

E2-based degraders have several differentiating features from conventional E3 approaches which include: a wider target scope due to a single E2 being able to act through multiple different E3s, broader and higher levels of E2 expression leads to a higher potential for efficacy, and a lower risk of innate or developed cross-resistance due to the lower E2 mutation rate.

BPGbio’s E2 Platform is First-In-Class

The BPGbio E2 Platform includes a proprietary library of >1,000 Ro3 fragments discovered by BPGbio that are potential ligands to a variety of E2 targets, proprietary ternary structures, a computational tool kit for E2 ligand design, and assays for rapidly attaining selectivity and specificity.

BPGbio Continues to Advance the Field

Strong, E2-specific binding for several BPGbio ligands has been observed via biophysical studies and high resolution structural biology. BPGbio has designed several CRBN-independent, orally available degraders with nanomolar potency and robust degradation to demonstrate the potential for developing E2-based therapeutics.

Molecular Glues for Neurology

The BPGbio Protein Homeostasis program also includes E2-based molecular glue leads for Huntingtin homeostasis and other neurological indications.