Topsalysin

Topsalysin, a first-in-class, pore-forming protein, is a highly potent ablative agent that is selective and targeted in that it is only activated by enzymatically active PSA which is found in high concentrations around prostate tumor cells and in the transition zone of the prostate. Topsalysin is in Phase 2 clinical development for the focal treatment of localized prostate cancer as well as Phase 3 clinical development for the treatment of the lower urinary tract symptoms of benign prostatic hyperplasia (BPH). More than 400 patients have received topsalysin, which continues to appear to be safe and well tolerated.

Topsalysin Mechanism of Action Video


A Highly Targeted Treatment

Topsalysin (PRX302) binds to the GPI-anchored receptors on the cell surface of prostate cells. Once activated by PSA, Topsalysin combines with other activated Topsalysin molecules, forming stable transmembrane pores that induce cell death. The prostate specific activation of Topsalysin by enzymatically active PSA thus limits exposure of non-prostate tissues to the drug’s activity, contributing to the safety of the therapy.

PRX302

Binding:

PRX302 dimers bind to GPI-anchored receptors and become concentrated on cell surface

Cleavage

Cleavage:

Active PSA cleaves tail, activating aerolysin on cell surface, exposing hydrophobic domains

Oligo

Oligomerization and pore formation:

Aerolysin assembles into a heptamer which forms a transmembrane pore

Cell Death

Cell Death:

Cell contents leak out causing cell death