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    DRUG CLASS:

    Immunoproteasome inhibitor

    Related drugs:
    5d
    ONX-0914 Suppresses Hormone-Sensitive Prostate Cancer by Promoting O-GlcNAcylation-Mediated Stabilization of TCF7L1. (PubMed, Oncol Res)
    This study identifies a novel ONX-0914/HBP/TCF7L1 O-GlcNAcylation axis that metabolically stabilizes TCF7L1, leading to repression of AR signaling and inhibition of HSPC progression. These findings reveal a previously unrecognized metabolic-transcriptional regulatory mechanism and highlight TCF7L1 O-GlcNAcylation as a potential therapeutic target in AR-dependent prostate cancer.
    Journal
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    PSMB8 (Proteasome 20S Subunit Beta 8) • TCF7 (Transcription Factor 7)
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    ONX 0914
    4ms
    Immunoproteasome inhibition triggers protein stress and apoptosis in cells of B cell lineage without impairing vaccination-induced antibody responses. (PubMed, Cell Death Discov)
    In this study, we used ONX 0914, an LMP7/LMP2-selective inhibitor of the IP, to study the effect of IP inhibition on B cells and antibody production...Furthermore, IP inhibition neither impaired vaccine-induced antibody responses, nor affected different B cell populations in two different vaccination models. These findings suggest that IP inhibition does not compromise vaccination efficacy and anti-viral humoral immunity, supporting the potential of IP-targeted therapies for autoimmune diseases.
    Preclinical • Journal
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    IFNG (Interferon, gamma) • PSMB8 (Proteasome 20S Subunit Beta 8)
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    ONX 0914
    10ms
    A Study of Zetomipzomib (KZR-616) in Patients With Autoimmune Hepatitis (PORTOLA) (clinicaltrials.gov)
    P2, N=24, Completed, Kezar Life Sciences, Inc. | Trial completion date: Aug 2025 --> Apr 2025 | Active, not recruiting --> Completed
    Trial completion • Trial completion date
    1year
    Phase 1b study of immunocytokine simlukafusp alfa (FAP-IL2v) combined with pembrolizumab for treatment of advanced and/or metastatic melanoma. (PubMed, Cancer Res Commun)
    The safety profile of FAP-IL2v in combination with pembrolizumab was manageable and consistent with the known safety profile. However, further exploration of FAP-IL2v and pembrolizumab was precluded in melanoma patients with prior CPI due to the lack of clinical activity.
    P1 data • Journal
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    CD8 (cluster of differentiation 8)
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    Keytruda (pembrolizumab) • simlukafusp alfa (RG7461)
    over1year
    A Study of Zetomipzomib (KZR-616) in Patients with Active Lupus Nephritis (PALIZADE) (clinicaltrials.gov)
    P2, N=84, Terminated, Kezar Life Sciences, Inc. | N=279 --> 84 | Trial completion date: Jul 2026 --> Nov 2024 | Suspended --> Terminated | Trial primary completion date: May 2026 --> Nov 2024; Sponsor Decision.
    Enrollment change • Trial completion date • Trial termination • Trial primary completion date
    over1year
    Phase 1b Study of the Immunocytokine Simlukafusp alfa (FAP-IL2v), in Combination with Cetuximab in Patients with Head and Neck Squamous Cell Carcinoma. (PubMed, Clin Cancer Res)
    The safety profile of FAP-IL2v in combination with cetuximab was acceptable and pharmacodynamic markers support the proposed mode-of-action of this combination, but the overall low antitumor activity does not warrant further clinical exploration in HNSCC. [Part C of Study BP29842 (NCT02627274).].
    P1 data • Journal • Combination therapy
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    CD8 (cluster of differentiation 8) • IL2RA (Interleukin 2 receptor, alpha) • ISG20 (Interferon Stimulated Exonuclease Gene 20)
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    Erbitux (cetuximab) • simlukafusp alfa (RG7461)
    over1year
    Phase 2 study of the antitumour activity and safety of simlukafusp alfa (FAP-IL2v) combined with atezolizumab in patients with recurrent and/or metastatic cervical squamous cell carcinoma. (PubMed, EBioMedicine)
    FAP-IL2v plus atezolizumab is clinically active and has manageable safety in patients with recurrent and/or metastatic cervical SCC.
    Clinical • P2 data • Preclinical • Retrospective data • Review • Journal • Metastases
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    PD-L1 (Programmed death ligand 1) • CD8 (cluster of differentiation 8)
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    PD-L1 expression • PD-L1 negative
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    Tecentriq (atezolizumab) • simlukafusp alfa (RG7461)
    over1year
    A Study of Zetomipzomib (KZR-616) in Patients With Active Lupus Nephritis (PALIZADE) (clinicaltrials.gov)
    P2, N=279, Suspended, Kezar Life Sciences, Inc. | Recruiting --> Suspended
    Trial suspension
    over1year
    A Study of Zetomipzomib (KZR-616) in Patients With Autoimmune Hepatitis (PORTOLA) (clinicaltrials.gov)
    P2, N=24, Active, not recruiting, Kezar Life Sciences, Inc. | Trial completion date: Mar 2025 --> Aug 2025 | Trial primary completion date: Sep 2024 --> Feb 2025
    Trial completion date • Trial primary completion date
    over1year
    A Study of Zetomipzomib (KZR-616) in Patients With Autoimmune Hepatitis (PORTOLA) (clinicaltrials.gov)
    P2, N=24, Active, not recruiting, Kezar Life Sciences, Inc. | Recruiting --> Active, not recruiting
    Enrollment closed
    over1year
    Enhancing the immunogenicity of Wilms tumor 1 epitope in mesothelioma cells with immunoproteasome inhibitors. (PubMed, PLoS One)
    These results suggest that ONX-0914 prevents the internal destructive cleavage of WT1235 by IP, thereby promoting the specific presentation of the WT1 epitope by MESO-4. In conclusion, selective IP inhibitors might offer a means to modulate cancer cell immunogenicity by directing the presentation of particular tumor epitopes.
    Journal
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    CD8 (cluster of differentiation 8) • WT1 (WT1 Transcription Factor)
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    ONX 0914
    almost2years
    Phase II study to determine the anti-tumor activity and safety of simlukafusp alfa (FAP-IL2v) combined with atezolizumab in esophageal cancer. (PubMed, Clin Cancer Res)
    P2; FAP-IL2v plus atezolizumab demonstrated clinical activity and was tolerable in patients with previously treated esophageal SCC.
    Journal • P2 data • PD(L)-1 Biomarker • IO biomarker
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    PD-L1 (Programmed death ligand 1)
    |
    PD-L1 expression • PD-L1 negative
    |
    VENTANA PD-L1 (SP263) Assay
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    Tecentriq (atezolizumab) • simlukafusp alfa (RG7461)