Androgen receptor degrader (non-ligand binding site)

Disease Need 

The androgen receptor (AR) is a ligand-dependent transcription factor that plays a crucial role in normal prostate development and homeostasis, but also in the progression of prostate cancer. Androgen deprivation therapy, which limits AR function, is initially effective for advanced or metastatic prostate cancer. For patients who relapse or progress following or during androgen deprivation therapy, cure is no longer an option. For these metastatic castrate-resistant prostate cancer (CPRC) patients, new treatment options are urgently needed. The vast majority of CRPC is driven by AR alterations in the form of mutations, amplifications, and truncations. The dependence of CRPC on AR has defined a clear unmet medical need.

Our Approach 

Our androgen receptor degrader is part of Parabilis’s disease-area focus on prostate cancer, and has synergies with our ERG degrader program. The AR degrader program targets the activated form of AR by binding at a different site from approved drugs, circumventing known resistance mutations. This novel mechanism of action provides a new tool to disrupt AR function, with potential for therapeutic benefit for AR-amplified and AR-mutant CRPC patients.