Shanghai, China---Shanghai Haihe Biopharma Co., Ltd (referred as “Haihe Biopharma” or the “Company”) today announced that the preliminary results from the Phase Ib Study of EZH1/2 Inhibitor HH2853 were presented at the oral section of the American Society of Hematology (ASH) Annual Meeting 2023 by the team of professor Tongyu Lin, the global leading principal investigator of the study, from Sichuan Cancer Hospital. This report presented the preliminary safety and efficacy data of HH2853 in patients with relapsed and/or refractory peripheral T-cell lymphoma (R/R PTCL).

Title: A Multicenter, Open-Label, Single-Arm, Phase Ib Clinical Trial of HH2853 in the Treatment of Patients with Relapsed and/or Refractory Peripheral T-Cell Lymphoma

Presenter: Huangming Hong, MD, a Member of Tongyu Lin’s Team, Sichuan Cancer Hospital

Section: Oral presentation

Abstract Number: 304

Presentation Time: December 09, 2023, 4:45 pm - 5:00 pm in USA

HH2853 is a novel, potent, and selective Zeste homolog 1 and 2 enhancer (EZH1/2) dual inhibitor that has demonstrated clinical benefit and a favorable safety profile in previous Phase I/II trials (HH2853-G101) in solid tumors and R/R non-Hodgkin lymphoma (NHL). Here, we report preliminary results from a Phase Ib trial of HH2853 in R/R PTCL.

HH2853-G202 (CTR20221416) is a multicenter, open-label, single-arm, phase Ib clinical trial to evaluate the efficacy and safety in the treatment of patients with R/R PTCL.

As of June 15, 2023, thirty seven patients were enrolled, including 34 R/R PTCL patients and 3 R/R NHL patients (non-PTCL pathological type). the most common TRAEs (≥10%) were PLT decreased (18 pts,48.6%) , anemia (19 pts, 51.4%)，and diarrhea (15 pts, 40.5%). The frequently reported TRAEs of grade ≥3 with an incidence of ≥10% were PLT decreased (5 pts, 13.5%), white blood cell count decreased (4 pts, 10.8%) and neutrophil count decreased (5 pts, 13.5%). The majority of TRAEs were reversible or clinically manageable, consistent with the safety profile observed in other clinical studies of HH2853. Among the 34 enrolled R/R PTCL patients, 28 patients had the evaluated response. The Overall Response Rate (ORR) is 64.7% (22 pts) and the Disease Control Rate (DCR) is 73.5% (25 pts). The detail information can be viewed in the ASH abstract.

The selective EZH1/2 dual inhibitor HH2853 demonstrated favorable safety and preliminary efficacy in R/R PTCL patients and is a potential new therapeutic option for R/R PTCL.

The American Society of Hematology (ASH) is one of the largest and most comprehensive international academic events in the field of hematology in the world. The academic reports presented at the ASH annual meeting represent the most important and cutting-edge research results in the field of hematology. Tens of thousands of hematology experts, scholars and industry stakeholders from nearly 100 countries and regions around the world attended the conference to share and discuss cutting-edge research progress, breakthrough clinical research results and valuable clinical practice experience.

Enhancer of zeste homolog 1/2 (EZH1/2) are the catalytic subunits of the polycomb repressive complex 2 (PRC2) complex, which can catalyze the trimethylation of histone H3 at lysine 27 (H3K27me3) to regulate the expression of multiple genes. EZH2 overexpression or gain-of-function mutations were reported in multiple tumor types and are closely related to tumor growth and metastasis 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 strategy for various types 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 inhibitors may have better therapeutic potential than EZH2 inhibitor. To date, no EZH2 or EZH1/2 inhibitors have been approved in China.

HH2853 is a selective EZH1/2 dual inhibitor, which can significantly reduce the overall H3K27me3 level in different types of cells and has potent antitumor activity against tumor cells with gain-of-function EZH2 mutation. It also has strong antitumor activity against some tumor cells with wild-type EZH2. In mouse xenograft models, HH2853 showed strong in vivo antitumor activity, which was superior to tazemetostat (the first marketed EZH2 inhibitor worldwide) at the same dose.

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, manufacturing 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 innovation with global perspective management and R&D team. Currently Haihe Biopharma has one approved product (Gumarontinib, Haiyitan®) in China and several drug candidates in the pipeline.