Shanghai, China---Shanghai Haihe Biopharma Co., Ltd (referred as "Haihe Biopharma" or the “Company”), today announced that the preliminary results of the first-in-human, open label, Phase I clinical study of EZH1/2 inhibitor HH2853 is selected for poster section at the American Association for Cancer Research (AACR) Annual Meeting 2023 in Orlando, Florida. This trial is to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics and preliminary clinical activity of HH2853, an EZH1/2 inhibitor, in patients with relapsed/refractory Non-Hodgkin’s lymphoma or advanced solid tumors.

Title: Preliminary results from the Phase I part of a first-in-human Phase I/II study of HH2853, an EZH1/2 inhibitor, in patients with relapsed/refractory non-Hodgkin lymphomas or advanced solid tumors
Lead Author: Lin Shen, Doctor of Medicine, Peking University Cancer Hospital
Content: Poster presentation
Abstract Presentation Number: CT105

HH2853-G101 study is a first-in-human, open-label, multi-center, phase I/II study of HH2853 in patients with relapsed/refractory (r/r) non-Hodgkin lymphomas (NHLs) or advanced solid tumors. Ph I consist of two parts: dose escalation and dose extension parts. Safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD) and preliminary anti-tumor activity of HH2853 were explored in this Ph I study.

As of Oct 19, 2022, a total of 57 patients, including 50 patients with solid tumors and 7 patients with r/r follicular lymphoma (FL), were enrolled from 12 sites in China and the US. Twenty-five (43.9%) patients received ≥3 lines of prior systemic therapies. Six dose levels（50 mg, 100 mg, 200 mg, 400 mg, 600 mg and 800 mg）were evaluated. DLTs were observed in 2 of 8 DLT evaluable patients at 800 mg: one grade 3 platelet count decreased and one grade 3 diarrhea. The maximal tolerated dose was not reached. The most common treatment-related adverse events (TRAE) were diarrhea (45.6%), blood bilirubin increased (35.1%), white blood cell count (WBC) decreased (26.3%), platelet count decreased (26.3%), rash (24.6%) and anemia (22.8%). The most common ≥grade 3 TRAEs included anemia (8.8%), platelet count decreased (7.0%), WBC decreased (5.3%) and diarrhea (5.3%). TRAEs leading to dose interruption or reduction were reported in 17.5% and 8.8% patients respectively. No TRAE led to dose discontinuation or death. PK data indicated dose-related increase in exposure from 50 to 600 mg. PD data showed a significant inhibition (maximum reached >90%) of H3K27me3 in granulocytes and monocytes at 400-800 mg. Tumor responses were observed in 7 patients from 200 to 800 mg in multiple tumor types, including complete response in 1 patient with FL, partial response in 3 patients with epithelioid sarcoma, 2 patients with FL and 1 patient with malignant rhabdoid tumor of pancreas.

This first-in-human study of HH2853 showed a manageable safety profile and promising anti-tumor activity in multiple tumor types.

The American Association for Cancer Research (AACR) was founded in 1907. The AACR is the first and largest cancer research organization dedicated to accelerating the conquest of cancer. The AACR has more than 50,000 members residing in 129 countries and territories. Membership includes 256 Fellows of the AACR Academy and 54 Nobel laureates. Through its programs and services, the AACR fosters research in cancer and related biomedical science; accelerates dissemination of new research findings among scientists and others dedicated to the conquest of cancer; promotes science education and training; and advances understanding of cancer etiology, prevention, diagnosis, and treatment throughout the world.

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. To date, no EZH2 or EZH1/2 inhibitors have been approved in China.

HH2853 is a potent and selective small molecule inhibitor targeting EZH1/2. In preclinical studies, HH2853 significantly reduced overall H3K27me3 level in cells, and exhibited 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. 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, focusing on the research, development, manufacturing and commercialization of innovative anti-tumor therapies. The Company aims to discover and deliver life-saving therapies to cancer patients world widely. As an R&D focused company led by an academician of the Chinese Academy of Engineering, Haihe Biopharma is committed to in-house innovation. The Company has a full R&D and management team with global perspectives and is proactively mapping out its global drug development strategy. The Company currently has one approved product (INN:Gumarontinib) in China and twelve drug candidates. As of today, Haihe Biopharma has received total 33 clinical trial approvals and has been conducting clinical trials in four major countries.