Hanmi Pharmaceutical's Dual EZH1/2 Inhibitor Shows Promising Antitumor Activity in Phase 1 Trial
核心洞察
Hanmi Pharmaceutical's HM97662, a next-generation dual EZH1 (搜索)/2 inhibitor, demonstrated manageable safety and initial antitumor activity in a Phase 1 clinical trial presented at ESMO 2025.
The study enrolled 28 patients with advanced solid tumors (搜索) across seven dose groups (50-350mg), with one uterine sarcoma (搜索) patient achieving partial response and one ovarian cancer (搜索) patient maintaining stable disease for over 15 months.
The dual inhibition mechanism targeting both EZH1 (搜索) and EZH2 (搜索) proteins aims to overcome resistance limitations of existing EZH2-selective inhibitors by more effectively blocking cancer cell growth pathways.
Hanmi Pharmaceutical has reported encouraging results from its Phase 1 clinical trial of HM97662, a next-generation dual EZH1 (搜索)/2 inhibitor designed to overcome resistance challenges faced by existing targeted cancer therapies. The Korean pharmaceutical company presented these findings at the European Society for Medical Oncology (ESMO) Congress 2025 in Berlin, demonstrating the drug's initial safety profile and antitumor activity in patients with advanced solid tumors (搜索).
Novel Dual Inhibition Strategy
HM97662 represents a significant advancement in targeted cancer therapy through its dual inhibition mechanism that simultaneously blocks both EZH1 (搜索) and EZH2 (搜索) proteins. These proteins function as "genetic regulatory switches" that play crucial roles in regulating cancer cell growth and differentiation. By controlling both proteins simultaneously, the drug aims to more effectively block the function of the Polycomb Repressive Complex 2 (搜索) (PRC2 (搜索)), thereby enhancing the suppression of cancer cell growth.
The dual approach addresses a critical limitation of existing EZH2 (搜索)-selective inhibitors. When only EZH2 is selectively inhibited, EZH1 (搜索) may become complementarily activated, potentially contributing to drug resistance. This compensatory mechanism has made the dual inhibition strategy targeting both EZH2 and EZH1 an increasingly promising therapeutic approach.
Phase 1 Clinical Trial Results
The Phase 1 study evaluated the safety, tolerability, and pharmacokinetic characteristics of HM97662 in 28 patients with advanced or metastatic solid tumors (搜索). Patients received once-daily doses across seven dose groups ranging from 50 to 350 mg. The study population consisted primarily of high-risk patients who had undergone four or more lines of standard therapy and had limited alternative treatment options.
HM97662 demonstrated a manageable safety profile without severe toxicity leading to treatment discontinuation or death. Notably, some patients experienced partial response (PR) and long-term stable disease (SD), indicating meaningful clinical activity.
Clinical Efficacy Outcomes
Two cases particularly highlighted the drug's antitumor potential. A patient with SMARCA4-deficient uterine sarcoma (搜索) receiving the 300mg dose achieved a partial response with a 39% tumor reduction according to RECIST v1.1 criteria. Additionally, an ovarian cancer (搜索) patient in the 200mg administration group maintained stable disease for over 15 months while experiencing up to a 26% reduction in tumor size.
According to the released abstract from the initial presentation, one patient with uterine sarcoma (搜索) showed partial remission with some cancer cells disappearing at the 300mg dose, while one patient with ovarian cancer (搜索) in the 200mg group maintained stable lesions that did not progress further for more than 14 months.
Expert Perspectives and Future Directions
Kim Beomseok, Professor of Hematology and Oncology at Seoul National University Hospital and lead investigator for the Phase 1 study, emphasized the significance of these results. "It is noteworthy that positive antitumor effects were observed in patients with advanced or metastatic solid tumors (搜索), with some patients achieving partial responses and maintaining long-term stable disease while continuing anticancer treatment," he stated.
Hanmi Pharmaceutical plans to expand its clinical development strategy by designing tailored combination therapy approaches that reflect the biological characteristics and molecular mutation profiles of different cancer types. Noh Youngsoo, Director of the ONCO Clinical Team at Hanmi Pharmaceutical, noted that the Phase 1 results validate the EZH1 (搜索)/2 dual inhibition strategy's transition from preclinical research to demonstrable clinical antitumor activity.
Broader Industry Context
The presentation of HM97662 results occurred alongside other significant developments from Korean pharmaceutical companies at ESMO 2025. The conference featured 283 sessions, 1,760 oral presentations, and 2,543 posters, with Korean companies including Alteogen, Riga Chem Biologics, and Lunit also showcasing their research competitiveness in the global clinical stage.
A company official from Hanmi Pharmaceutical explained that the dual-target strategy to inhibit EZH1 (搜索) and EZH2 (搜索) simultaneously has shown potential to solve the resistance problem of existing treatments. The company plans to release additional results from the 350mg high-dose group as part of its ongoing clinical development program.