HY809382 / Yangtze River Pharmaceutical Group - LARVOL DELTA

HY809382, a PRC2 degrader with best-in-class properties, demonstrates efficacy across multiple tumors and overcomes EZH2 inhibitor clinical resistance caused by EZH2 genetic mutations (AACR 2026) - "Among various EZH2 inhibitors under development, Tazemetostat (Tazverik) was the first to received FDA approval for the treatment of follicular lymphoma (FL) and epithelioid sarcoma (ES)...Under identical experimental conditions, HY809382 exhibited greater potency than both PF-06821497 (an EZH2 inhibitor) and APG-5918 (an EED inhibitor)...Furthermore, HY809382 combined with enzalutamide synergistically suppressed tumor growth in a castration-resistant prostate cancer xenograft model. Clinically identified EZH2 mutations confer resistance to FDA-approved EZH2 inhibitors, whereas HY809382 remained effective in both cellular and in vivo xenograft models. Collectively, these data support HY809382 as a promising best-in-class PRC2 degrader candidate, warranting further development for the treatment of tumors exhibiting clinical resistance to EZH2 inhibitors."

Clinical • Castration-Resistant Prostate Cancer • Clear Cell Renal Cell Carcinoma • Endometrial Cancer • Follicular Lymphoma • Gastric Adenocarcinoma • Gastric Cancer • Genito-urinary Cancer • Hematological Malignancies • Lung Cancer • Lymphoma • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Prostate Cancer • Sarcoma • Soft Tissue Sarcoma • Solid Tumor • EZH2

Preclinical characterization of HY809382, a highly potent and orally bioavailable PRC2 PROTAC, for the treatment of lymphoma and solid tumors (AACR 2026) - "Although targeting EZH2 has been the primary approach in PRC2 inhibitor development, leading to the FDA approval of Tazemetostat as the first-in-class agent, no PRC2 degraders have yet progressed to clinical trials. Preliminary non-GLP repeated-dose toxicity studies in mice and cynomolgus monkeys indicated that HY809382 was well tolerated, with estimated therapeutic windows of >95 and >25, respectively. These findings support the potential of HY809382 as a best-in-class PRC2 degrader and warrant its further evaluation in IND-enabling studies."

Preclinical • Diffuse Large B Cell Lymphoma • Genito-urinary Cancer • Hematological Malignancies • Lymphoma • Oncology • Prostate Cancer • Rhabdoid Tumor • Sarcoma • Solid Tumor • CRBN • EZH2 • GSPT1 • IKZF1 • SUZ12