OncoPSMA-GlyPro-MMAE is a small molecule drug conjugate with ultra high affinity for Prostate Specific Membrane Antigen (PSMA), a protein highly overexpressed in prostate cancer. OncoPSMA-GlyPro-MMAE consists of (i) a small organic ligand targeting PSMA, (ii) an innovative cleavable GlycineProline linker, and (iii) the cytotoxic payload monomethyl auristatine E (MMAE).
The cytotoxic payload MMAE is inactive when bound to OncoPSMA via the GlycineProline linker.
Proteases in the tumor microenvironment cleave the linker, thereby releasing the now active MMAE. Using mass spectrometry methodologies, we confirmed in mouse models of prostate cancer that OncoPSMA-GlyPro-MMAE selectively delivers MMAE to the tumor while showing extremely low uptake and release in healthy organs. This efficient release of MMAE in the tumor microenvironment coincided with a potent anti-tumor activity.
A first-in-human clinical trial with OncoPSMA-GlyPro-MMAE in patients with prostate cancer is expected to start in 2025.
