HH2853 / HaiHe Biopharma, Shanghai Inst. of Materia Medica - LARVOL DELTA

A multicenter, open-label, single-arm, phase Ib clinical trial of HH2853 treatment in patients with relapsed and/or refractory peripheral T-cell lymphoma. (PubMed, J Hematol Oncol) - P1/2 | "The selective EZH1/2 dual inhibitor HH2853 demonstrated acceptable and manageable safety profiles and promising efficacy in r/r PTCL patients, indicating its therapeutic potential for this difficult-to-treat patient population."

Journal • P1 data • Hematological Disorders • Hematological Malignancies • Leukopenia • Lymphoma • Oncology • Peripheral T-cell Lymphoma • Solid Tumor • T Cell Non-Hodgkin Lymphoma • Thrombocytopenia • EZH2

Study to Evaluate Efficacy and Safety of HH2853 in Relapsed/Refractory Peripheral T-cell Lymphoma (clinicaltrials.gov) - P1/2 | N=100 | Recruiting | Sponsor: Haihe Biopharma Co., Ltd.

New P1/2 trial • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Peripheral T-cell Lymphoma • T Cell Non-Hodgkin Lymphoma

Dual-target EZH2 inhibitor: latest advances in medicinal chemistry. (PubMed, Future Med Chem) - "Dual-target inhibitors, exemplified by EZH1/2 inhibitor HH-2853(28), offer enhanced efficacy and reduced adverse effects. This review highlights recent advancements in dual inhibitors targeting EZH2 and other proteins like BRD4, PARP1, and EHMT2, emphasizing rational design, structure-activity relationships, and safety profiles, suggesting their potential in clinical applications."

Journal • Review • Oncology • BRD4 • EHMT2 • EZH2 • PARP1

Evaluate the Safety and Clinical Activity of HH2853 (clinicaltrials.gov) - P1/2 | N=254 | Recruiting | Sponsor: Haihe Biopharma Co., Ltd. | N=168 ➔ 254

Enrollment change • Metastases • Follicular Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Peripheral T-cell Lymphoma • Sarcoma • Soft Tissue Sarcoma • Solid Tumor • T Cell Non-Hodgkin Lymphoma • ARID1A • BAP1

Evaluate the Safety and Clinical Activity of HH2853 (clinicaltrials.gov) - P1/2 | N=168 | Recruiting | Sponsor: Haihe Biopharma Co., Ltd. | Trial completion date: Dec 2024 ➔ Dec 2025 | Trial primary completion date: Dec 2023 ➔ Dec 2025

Metastases • Trial completion date • Trial primary completion date • Follicular Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Solid Tumor • ARID1A • BAP1

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 (ASH 2023) - "The 6-month OS rates was 91.97% (95%CI: 71.50%, 97.93%). Conclusions The selective EZH1/2 dual inhibitor HH2853 demonstrated good safety and promising efficacy in r/r PTCL patients, indicating its potential as a therapeutic option for this difficult to treat patient population."

Clinical • P1 data • Anemia • Bone Marrow Transplantation • Hematological Disorders • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Peripheral T-cell Lymphoma • Solid Tumor • T Cell Non-Hodgkin Lymphoma • Transplantation • EZH2

HH2853, an EZH1/2 inhibitor, in patients with epithelioid sarcoma: Preliminary results from the phase 1 part of a first-in-human phase I/II study. (ASCO 2023) - P1/2 | "Tazemetostat (an EZH2 inhibitor) has been approved by FDA for clinical use in ES. HH2853 showed an acceptable safety profile and promising anti-tumor activity in heavily pretreated ES pts with a wide therapeutic window, providing evidence for further investigation. Clinical trial information: NCT04390737."

Clinical • P1/2 data • Anemia • Diabetes • Hematological Disorders • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Sarcoma • Soft Tissue Sarcoma • Solid Tumor • EZH2

Dysregulation of iron homeostasis by TfR-1 renders EZH2 wild type diffuse large B-cell lymphoma resistance to EZH2 inhibition. (PubMed, Acta Pharmacol Sin) - "We have discovered a novel EZH1/2 inhibitor HH2853 with a better antitumor effect than EPZ-6438 in preclinical studies. On the other hand, EZH2i impaired the occurrence of ferroptosis by upregulating the heat shock protein family A (Hsp70) member 5 (HSPA5) and stabilizing glutathione peroxidase 4 (GPX4), a ferroptosis suppressor; co-treatment with ferroptosis inducer erastin effectively overrode the resistance of DLBCL to EZH2i in vitro and in vivo. Altogether, this study reveals iron-dependent resistance evoked by EZH2i in DLBCL cells, and suggests that combination with ferroptosis inducer may be a promising therapeutic strategy."

Journal • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Sarcoma • Soft Tissue Sarcoma • Solid Tumor • EZH2 • GPX4 • HSPA5 • MYC

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 (AACR 2023) - P1/2 | "HH2853 is a novel selective EZH1/2 dual inhibitor, which has demonstrated superior anti-tumor efficacy to tazemetostat (EZH2 inhibitor approved by FDA) in various preclinical models. This is a first-in-human, open-label, multi-center, phase (Ph) I/II study of HH2853 in patients (pts) with relapsed/refractory (r/r) non-Hodgkin lymphomas (NHLs) or advanced solid tumors. This first-in-human study of HH2853 showed a manageable safety profile and promising anti-tumor activity in multiple tumor types, supporting further exploration in NHLs and solid tumors after recommended Ph II dose is determined.Clinical trial information: NCT04390737"

Clinical • Metastases • P1/2 data • Follicular Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Pancreatic Cancer • Rhabdoid Tumor • Sarcoma • Soft Tissue Sarcoma • Solid Tumor • EZH2

Valemetostat: First approval as a dual inhibitor of EZH1/2 to treat adult T-cell leukemia/lymphoma. (PubMed, Drug Discov Ther) - "Adult T-cell leukemia/lymphoma (ATL) is a mature T-cell lymphoma with a poor prognosis. Several other dual EZH1/2 inhibitors such as HH2853, HM97594, and HM97662 have also demonstrated potential in treating malignant tumors. Dual targeting EZH1/2 may have promising antitumor action in hematological malignancies and solid tumors."

Journal • Adult T-Cell Leukemia-Lymphoma • Hematological Disorders • Hematological Malignancies • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Peripheral T-cell Lymphoma • Solid Tumor • T Cell Non-Hodgkin Lymphoma • EZH2

Evaluate the Safety and Clinical Activity of HH2853 (clinicaltrials.gov) - P1/2 | N=188 | Recruiting | Sponsor: Haihe Biopharma Co., Ltd. | Phase classification: P1 ➔ P1/2 | N=30 ➔ 188 | Trial completion date: Jun 2023 ➔ Dec 2024 | Trial primary completion date: Jun 2022 ➔ Dec 2023

Enrollment change • Phase classification • Trial completion date • Trial primary completion date • Follicular Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Solid Tumor • ARID1A • BAP1

HH2853 is a selective small molecular dual inhibitor of EZH1/2 with potent anti-tumor activities (AACR 2022) - "The potency and selectivity of HH2853 against EZH1/2 were assessed at biochemical and cellular levels, and its anti-tumor activities were evaluated in multiple tumor models in vitro and in vivo in comparison with FDA-approved EZH2 selective inhibitor tazemetostat. Taken together, HH2853 is a selective EZH1/2 dual inhibitor with potent anti-tumor activities and favorable PK properties. HH2853 is currently in phase I clinical development."

Hematological Malignancies • Oncology • EZH2

Evaluate the Safety and Clinical Activity of HH2853 (clinicaltrials.gov) - P1; N=30; Recruiting; Sponsor: Haihe Biopharma Co., Ltd.; Trial completion date: Dec 2021 ➔ Jun 2023; Trial primary completion date: Jun 2021 ➔ Jun 2022

Clinical • Trial completion date • Trial primary completion date • Follicular Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Solid Tumor

A Phase I Study to Evaluate the Safety and Clinical Activity of HH2853. (clinicaltrials.gov) - P1; N=30; Recruiting; Sponsor: ShangHai HaiHe Pharmaceutical; Trial completion date: Aug 2021 ➔ Dec 2021; Trial primary completion date: Mar 2021 ➔ Jun 2021

Clinical • Trial completion date • Trial primary completion date • Follicular Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Solid Tumor

A Phase I Study to Evaluate the Safety and Clinical Activity of HH2853. (clinicaltrials.gov) - P1; N=30; Recruiting; Sponsor: ShangHai HaiHe Pharmaceutical; Not yet recruiting ➔ Recruiting

Enrollment open • Follicular Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Solid Tumor

A Phase I Study to Evaluate the Safety Tolerability, Pharmacokinetics and Clinical Activity of HH2853 (clinicaltrials.gov) - P1; N=30; Not yet recruiting; Sponsor: ShangHai HaiHe Pharmaceutical

Clinical • New P1 trial • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Gastrointestinal Cancer • Hematological Disorders • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology