^
    5ms
    Evaluate the Safety and Clinical Activity of HH2853 (clinicaltrials.gov)
    P1/2, N=254, Recruiting, Haihe Biopharma Co., Ltd. | Trial completion date: Dec 2025 --> Dec 2028 | Trial primary completion date: Dec 2025 --> Dec 2027
    Trial completion date • Trial primary completion date • First-in-human
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    ARID1A (AT-rich interaction domain 1A) • BAP1 (BRCA1 Associated Protein 1)
    |
    ARID1A mutation • EZH2 mutation
    |
    HH2853
    9ms
    Study to Evaluate Efficacy and Safety of HH2853 in Relapsed/Refractory Peripheral T-cell Lymphoma (clinicaltrials.gov)
    P1/2, N=100, Recruiting, Haihe Biopharma Co., Ltd. | Trial primary completion date: Apr 2025 --> Oct 2025
    Trial primary completion date
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    HH2853
    10ms
    Safety and efficacy of HH2853, a novel EZH1/2 dual inhibitor, in patients with refractory solid tumours or non-Hodgkin lymphomas: a phase I study. (PubMed, EClinicalMedicine)
    HH2853 is a novel dual EZH1/2 inhibitor that exhibits superior antitumour activity compared to tazemetostat across various preclinical models. A phase II trial of HH2853 in patients with ES is underway. The Science, Technology and Economic Commission of Shanghai Pudong New Area Municipality and Shanghai Haihe Biopharma Co., Ltd.
    P1 data • Journal
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    EZH2 (Enhancer of zeste 2 polycomb repressive complex 2 subunit)
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    Tazverik (tazemetostat) • HH2853
    1year
    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)
    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.
    P1 data • Journal
    |
    EZH2 (Enhancer of zeste 2 polycomb repressive complex 2 subunit)
    |
    HH2853
    1year
    Study to Evaluate Efficacy and Safety of HH2853 in Relapsed/Refractory Peripheral T-cell Lymphoma (clinicaltrials.gov)
    P1/2, N=100, Recruiting, Haihe Biopharma Co., Ltd.
    New P1/2 trial
    |
    HH2853
    almost2years
    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.
    Review • Journal • PARP Biomarker
    |
    EZH2 (Enhancer of zeste 2 polycomb repressive complex 2 subunit) • PARP1 (Poly(ADP-Ribose) Polymerase 1) • BRD4 (Bromodomain Containing 4)
    |
    HH2853
    2years
    Evaluate the Safety and Clinical Activity of HH2853 (clinicaltrials.gov)
    P1/2, N=254, Recruiting, Haihe Biopharma Co., Ltd. | N=168 --> 254
    Enrollment change • Metastases
    |
    ARID1A (AT-rich interaction domain 1A) • BAP1 (BRCA1 Associated Protein 1)
    |
    ARID1A mutation • BAP1 mutation • EZH2 mutation • SMARCA4 mutation
    |
    HH2853
    over2years
    Evaluate the Safety and Clinical Activity of HH2853 (clinicaltrials.gov)
    P1/2, N=168, Recruiting, Haihe Biopharma Co., Ltd. | Trial completion date: Dec 2024 --> Dec 2025 | Trial primary completion date: Dec 2023 --> Dec 2025
    Trial completion date • Trial primary completion date • Metastases
    |
    ARID1A (AT-rich interaction domain 1A) • BAP1 (BRCA1 Associated Protein 1)
    |
    ARID1A mutation • BAP1 mutation • EZH2 mutation • SMARCA4 mutation
    |
    HH2853
    over2years
    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
    |
    EZH2 (Enhancer of zeste 2 polycomb repressive complex 2 subunit)
    |
    HH2853
    3years
    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
    |
    MYC (V-myc avian myelocytomatosis viral oncogene homolog) • EZH2 (Enhancer of zeste 2 polycomb repressive complex 2 subunit) • GPX4 (Glutathione Peroxidase 4) • HSPA5 (Heat Shock Protein Family A (Hsp70) Member 5)
    |
    EZH2 wild-type
    |
    Tazverik (tazemetostat) • erastin • HH2853
    3years
    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)
    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
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    EZH2 (Enhancer of zeste 2 polycomb repressive complex 2 subunit)
    |
    Tazverik (tazemetostat) • HH2853
    over3years
    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)
    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 • P1/2 data • Metastases
    |
    EZH2 (Enhancer of zeste 2 polycomb repressive complex 2 subunit)
    |
    Tazverik (tazemetostat) • HH2853