Prostate cancer is the second most commonly occurring cancer in men and the fourth most commonly occurring cancer overall. Androgen deprivation therapy (ADT), which lowers the level of testosterone, has been the standard of care for this cancer across different stages. Initial ADT achieves responses in nearly all patients; however, the vast majority of responsive patients will ultimately become resistant, resulting in a poor prognosis for men diagnosed with this devastating condition. Castration-resistant prostate cancer (CRPC) is a form of advanced prostate cancer. With CRPC, the cancer no longer completely responds to ADT. Currently, enzalutamide and abiraterone, which are the 2nd generation of ADT, have been beneficial for some patients, but resistance mechanisms reduce their efficacy, including increased levels of androgen production, increased AR gene, and enhancer expression, AR point mutations, and alternative slicing AR variants.

We are developing ICX-301, a potent, selective, and orally available small-molecule inhibitor of the pan-AR to treat prostate cancers. It does not involve testosterone but instead travels to the region where the Androgen receptor binds to its DNA and disrupts their interaction. No matter whether the AR is with its ligand or not, it blocks the last entry gate to the DNA binding site and can simply silence the transcriptional activity.

In vitro and in vivo studies show it reduces the expression level of major target proteins, PSAs, and leads to cell growth inhibition. By inhibiting AR binding to DNA directly, it doesn’t need to destroy the AR protein nor intercalate into the DNA, so there is no concern of compensating feedback in AR protein expression or non-specific DNA intercalation. 

ICX-301 was selected for the KDDF(Korea Drug Development Fund) national project in 2023 and plans to focus on developing candidate drugs. We plan to optimize our leads and initiate a GLP study in 2nd half of 2024.