[Press Release] On October 22, Hanmi announced that its investigational targeted anticancer therapy, HM97662, a novel EZH1/2 dual inhibitor, demonstrated a favorable safety profile and encouraging early antitumor activity in a first-in-human Phase 1 study, marking a meaningful step forward in its global clinical development.

Hanmi Pharmaceutical participated in the European Society for Medical Oncology (ESMO) Congress 2025, held in Berlin, Germany, from October 17 to 21, where the company presented Phase 1 data on HM97662 through a scientific poster session.

HM97662 is an innovative targeted therapy that inhibits both EZH1 and EZH2 proteins through a dual-inhibition mechanism. This approach offers enhanced anti-tumor efficacy and potential to overcome EZH2 inhibitor-mediated resistance.

Often referred to as “key epigenetic regulators,” EZH1 and EZH2 play critical roles in the development, progression, and differentiation of malignant tumors. By simultaneously blocking both proteins, HM97662 is believed to effectively suppress the activity of the Polycomb Repressive Complex 2 (PRC2), a key oncogenic complex, thereby delivering potent and sustained anti-tumor effects.

Previous studies have shown that selective inhibition of EZH2 alone may lead to compensatory activation of EZH1, which can drive drug resistance. Accordingly, dual inhibition of both EZH2 and EZH1 has emerged as a promising therapeutic strategy to overcome this limitation.

Although EZH2-selective inhibitors have demonstrated clinical potential, emerging evidence suggests that EZH1 can functionally compensate for EZH2 depletion, potentially leading to limited therapeutic efficacy. Accordingly, dual inhibition of both EZH1 and EZH2 has attracted attention as a more promising therapeutic strategy to enhance anti-tumor activity by preventing compensatory mechanisms. 

At ESMO 2025, Hanmi presented Phase 1 clinical data evaluating the safety, tolerability, and pharmacokinetics of HM97662 in patients with advanced or metastatic solid tumors, where preliminary signs of antitumor activity were also observed. A total of 28 patients were enrolled and administered once-daily oral doses ranging from 50 to 350 mg across seven dose levels. The median number of prior treatment was four (range: 0-7), with most patients heavily pretreated and representing a high-risk population with limited therapeutic options. 

HM97662 demonstrated a manageable safety profile, with no treatment discontinuations or deaths due to treatment-emergent adverse events. Notably, clinical benefits, including partial response (PR) and durable stable disease (SD), were observed in some patients.

Among key case reports, a patient with SMARCA4-deficient uterine sarcoma achieved a confirmed partial response (PR) per RECIST v1.1 at 300 mg QD, with tumor shrinkage of -39% at cycle 5. In addition, a patient with ovarian cancer achieved prolonged stable disease (SD) at 200 mg QD, remaining on treatment for over 15 months with a maximum tumor reduction of -26%.

Professor Bhumsuk Keam, a coordinating investigator of the Phase 1 trial and medical oncologist at Seoul National University Hospital, stated, “The observation of meaningful anti-tumor activity in heavily pretreated patients with advanced or metastatic solid tumors is highly encouraging. The report of partial response and durable disease stabilization suggests promising therapeutic potential for HM97662 across multiple tumor types.”

The global Phase 1 clinical trial of HM97662, currently underway in South Korea and Australia, is progressing smoothly and continues to evaluate its safety and tolerability in patients with advanced or metastatic solid tumors. Hanmi also plans to develop biomarker-informed combination strategies based on tumor biology and molecular alteration profiles, aiming to build a robust body of clinical evidence to support future development.

Dr. Young Su Noh, Head of Hanmi’s ONCO Clinical Research Team, commented, “The Phase 1 results of HM97662 are highly meaningful, as they suggest that the EZH1/2 dual inhibition strategy, previously validated in preclinical studies, can also demonstrate anti-tumor activity in clinical settings. We believe HM97662 has the potential to expand into multiple cancer indications and help establish a new paradigm in targeted cancer therapy.”