Hinova Pharmaceuticals (SHA: 688302), a biopharmaceutical company based in China, is poised to present data from the first-in-human, non-randomized, open-label, multi-center Phase I dosage escalation study of its drug candidate HP518 at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting. HP518 is an androgen receptor (AR)-targeted PROteolysis TArgeting Chimera (PROTAC) drug under development for the treatment of metastatic castration-resistant prostate cancer (mCRPC).
As of April 22, 2024, the study had enrolled a total of 22 patients, who received daily doses of HP518 ranging from 25mg to 500mg. The patient cohort included 10 patients (45.5%) with a baseline ECOG score of 0 and 12 patients (54.5%) with a score of 1. The median number of prior treatment lines was 3.5 (ranging from 2 to 6). Following treatment with HP518, 3 patients exhibited a PSA50 response, and 2 patients achieved partial remission (PR) as confirmed by RECIST 1.1 criteria. The duration of efficacy was 36 weeks and 60 weeks, respectively, with one subject experiencing an 80% reduction in liver lesions. The median time to peak blood drug concentration after multiple oral doses of HP518 was between 3 to 12 hours, demonstrating favorable safety characteristics and no dose limiting toxicity (DLT) observed.
HP518 works by promoting the binding of AR and E3 ligase to form a ternary complex, leading to the ubiquitination of AR. This process leverages the intracellular ubiquitin proteasome system to degrade AR, reducing the protein expression level of AR in prostate cancer cells and inhibiting the growth of AR-dependent prostate cancer cells, thus offering a potential therapeutic approach for treating prostate cancer.- Flcube.com
