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 dimers bind to GPI-anchored receptors and become concentrated on cell surface
Active PSA cleaves tail, activating aerolysin on cell surface, exposing hydrophobic domains
Oligomerization and pore formation:
Aerolysin assembles into a heptamer which forms a transmembrane pore
Cell contents leak out causing cell death