Qilu Pharmaceutical has presented initial Phase I data for proteolysis-targeting chimera (PROTAC) androgen receptor (AR) degrader QLH12016 at the European Society for Medical Oncology (ESMO) 2025 congress, showing 7.4 month median radiographic progression-free survival (rPFS) in 36 patients with metastatic castration-resistant prostate cancer (mCRPC). The oral candidate demonstrated promising efficacy across dose levels from 100mg to 1200mg daily, including 9.0 month rPFS at 600mg dosing, with activity observed in both ligand-binding domain wild-type and mutant populations. Safety profile showed 91.7% treatment-related adverse events (TRAE) incidence, with 38.9% grade three or higher events (primarily anaemia and fatigue) without dose-limiting toxicities observed.

QLH12016 represents a novel approach to overcoming AR resistance mechanisms through targeted protein degradation versus conventional receptor antagonism. The PROTAC design utilises bifunctional molecules recruiting E3 ubiquitin ligase to induce AR ubiquitination and proteasomal degradation. Qilu's candidate joins an emerging class of protein degraders addressing the limitations of current antiandrogen therapies in mCRPC, where treatment options remain limited following resistance development to enzalutamide and abiraterone.

PharmCube's NextBiopharm® database lists 35 AR-targeting PROTAC developers globally, with BMS in the lead with the only late-stage candidate. Click here to request a free trial for NextBiopharm®.