Shanghai, Mar 31, 2023, Haihe Biopharma Co., Ltd. (hereby referred to as "Haihe Biopharma" or the “Company”) - focused on the discovery, development and commercialization of innovative oncology drugs, announces first patient dosed in phase II part of a phase I/II multi-center clinical trial of EZH1/2 inhibitor HH2853 in China, Haihe Biopharma’s de novo developed innovative drug with global rights.

This trial is a first-in-human, open label, phase I/II study to evaluate the safety, tolerability, pharmacokinetics and clinical activity of HH2853, an EZH1/2 inhibitor, in patients with relapsed/refractory non-Hodgkin’s lymphomas or advanced solid tumors.

Enhancer of zeste homolog 1/2 (EZH1/2) are the catalytic subunit of the polycomb repressive complex 2 (PRC2) complex. EZH2 is the catalytic subunit of the PRC2 complex, which can catalyze the trimethylation of lysine 27 of histone H3 (H3K27me3) to regulate the expression of multiple genes. EZH2 is highly expressed or gain-of-function mutated in many tumor types and is closely related to the proliferation, metastasis, invasion of tumor cells as well as poor prognosis. Furthermore, there is an evolutionarily conserved antagonistic relationship between PRC2 and the SWItch/Sucrose Non-Fermentable (SWI/SNF) complex. Deficiencies or mutations in the core subunits of SWI/SNF complex may weaken its resistance to PRC2 and promote tumor development. Consequently, targeting EZH1/2 is a potential therapeutic prospect in a variety of hematological and solid tumors. EZH1 is the homologous protein of EZH2, with compensatory effects to the function of EZH2. As a result, EZH1/2 dual-targeted inhibitors have better therapeutic potential.

HH2853 is a potent and selective small molecule inhibitor targeting EZH1/2. Preclinical results show that HH2853 can significantly reduce the overall H3K27me3 level in cells, and exhibits potent anti-tumor activity against peripheral T-cell lymphoma (PTCL), diffuse large B-cell lymphoma (DLBCL) harboring EZH2 mutation and various solid tumor models harboring mutations in the subunits of SWI/SNF complex both in vitro and in vivo. At the same dose, the anti-tumor activity of HH2853 is better than tazemetostat. Phase I clinical data show that HH2853 has good safety and pharmacokinetic characteristics, and has demonstrated preliminary efficacy in multiple doses of multiple tumor types.

Haihe Biopharma Co., Ltd is a global, values-based, R&D driven biopharmaceutical leader headquartered in China with operation centers in the US and Japan, and mainly focuses on innovative anti-tumor therapies. The company has the fully capability of drug discovery, development, manufacture and commercialization and delivers life-saving therapies to cancer patients in China, even the world widely. As an R&D focused company led by an academician of the Chinese Academy of Engineering, Haihe Biopharma is committed in-house innovator with global perspective management and R&D team. Currently Haihe Biopharma has one approved product (INN:Gumarontinib) in China and twelve drug candidates and total 33 clinical trials approved by authorities, and has been conducting clinical trials in four major countries.