Jing Medicine's embryonic ectoderm development (EED) inhibitor HJM-353 recently obtained approvals for clinical trials in both China and the United States. This is a major milestone in the transformation project signed between ShanghaiTech and Jing Medicine in 2019. It is also the first time that a transformation project of ShanghaiTech obtained approvals for clinical trials in both China and the United States.
**The following contents are from the website of Jing Medicine
Recently, Jing Medicine announced that its HJM-353, a novel EED protein inhibitor, has been approved for clinical trials by both the U.S. Food and Drug Administration (FDA) and the Center for Drug Evaluation (CDE) of China’s National Medical Products Administration (NMPA). Jing Medicine plans to carry out phase I clinical trials in patients with advanced hematological malignancies and solid tumors.
Polycomb repressive complex 2 (PRC2) is a histone methyltransferase complex composed of three core subunits: EZH2 (or EZH1), EED, and SUZ12. Studies have shown that PRC2 dysregulation is associated with the occurrence, progression, and poor prognosis of hematopoietic malignancies and solid tumors. EZH2 is overexpressed or has gain-of-function mutations in a variety of cancers, and the role of EZH2 inhibitors in cancer treatment has been clinically verified. However, the acquired drug resistance caused by secondary mutations of EZH2 limits the clinical application of such inhibitors. Meanwhile, EED can allosterically regulate the activity of EZH2 and plays an important role in stabilizing the structure of PRC2 complex. While acting similarly to EZH2 inhibitors, EED inhibitors are unaffected by EZH2 drug-resistant mutations and can simultaneously inhibit EZH1 activity, thus offering the possibility of a targeted therapy with longer-term efficacy.
HJM-353 is a novel, potent, and highly selective EED inhibitor with oral activity. It was developed by Jing Medicine in collaboration with ShanghaiTech University. By blocking trimethylation of histone H3 lysine 27 (H3K27me3), HJM-353 binds to EED and disrupts the H3K27me3-EED-EZH2 interaction, thereby inhibiting the enzymatic activity of PRC2. HJM-353 has favorable pharmacokinetic properties, good oral bioavailability, and a large safety window in various animal species. Preclinical studies have shown that HJM-353 has good anti-tumor activity in multiple tumor cells and animal models, and it is also effective against Tazemetostat-resistant strains.
The approval of the clinical trial applications for HJM-353 in both China and the United States reflects Jing Medicine’s global innovation capabilities, said Dr. Zeng Li, CEO of Jing Medicine. “HJM-353 has a novel mechanism of action, showing strong antitumor activity in vitro and in vivo. We look forward to further exploring its clinical efficacy and bringing clinical benefits to patients as soon as possible.