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    DRUG:

    zelenirstat (PCLX-001)

    i
    Other names: PCLX-001
    Company:
    Pacylex Pharmaceuticals
    Drug class:
    NMT inhibitor
    Related drugs:
    5ms
    Elucidating the role of N-myristoylation in the excessive membrane localization of PD-L1 in hypoxic cancers and developing a novel NMT1 inhibitor for combination with immune checkpoint blockade therapy. (PubMed, J Exp Clin Cancer Res)
    These findings provide robust theoretical support for the translational application of combining NMT1 inhibitors and ICB therapy in cancers under hypoxic conditions. This study introduces a combined cancer therapy strategy named "spatial blockade plus signaling inhibition of PD-L1.".
    Retrospective data • Journal • Checkpoint inhibition • PD(L)-1 Biomarker • IO biomarker
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    PD-L1 (Programmed death ligand 1) • HIF1A (Hypoxia inducible factor 1, alpha subunit)
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    PD-L1 expression
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    zelenirstat (PCLX-001)
    8ms
    Study of PCLX-001 in R/R Advanced Solid Malignancies and B-cell Lymphoma (clinicaltrials.gov)
    P1, N=29, Completed, Pacylex Pharmaceuticals | Recruiting --> Completed | N=60 --> 29
    Trial completion • Enrollment change
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    CD20 (Membrane Spanning 4-Domains A1)
    |
    zelenirstat (PCLX-001)
    9ms
    Study of Oral PCLX-001 in R/R Acute Myeloid Leukemia (clinicaltrials.gov)
    P1, N=35, Recruiting, Pacylex Pharmaceuticals | Not yet recruiting --> Recruiting
    Enrollment open
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    zelenirstat (PCLX-001)
    1year
    Study of Oral PCLX-001 in R/R Acute Myeloid Leukemia (clinicaltrials.gov)
    P1, N=35, Not yet recruiting, Pacylex Pharmaceuticals
    New P1 trial
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    zelenirstat (PCLX-001)
    over1year
    Phase I Trial of PCLX-001 in R/R Advanced Solid Malignancies and B-cell Lymphoma (clinicaltrials.gov)
    P1, N=60, Recruiting, Pacylex Pharmaceuticals | Trial primary completion date: Feb 2024 --> Oct 2024
    Trial primary completion date • Metastases
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    CD20 (Membrane Spanning 4-Domains A1)
    |
    CD20 expression
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    zelenirstat (PCLX-001)
    2years
    A First-in-Human, Open-Label, Phase I Dose Escalation Trial of Daily Oral Nmt Inhibitor Zelenirstat in Patients with Relapsed/Refractory B-Cell Lymphomas and Advanced Solid Tumors (ASH 2023)
    Zelenirstat (PCLX-001) is an oral, highly bioavailable, small molecule NMT inhibitor with strong affinity for both NMT1 and NMT2 proteins (IC 50 of 5nM and 8nM, respectively)...Additional pts, including a phase IIA study in pts with R/R B-cell NHL, are accruing at this dose for further safety and activity exploration. The absence of severe toxicities, attainment of plasma concentrations highly active in preclinical models, and early evidence of antitumor activity support the ongoing development of zelenirstat for pts with R/R B-cell lymphomas and advanced solid tumors.
    Clinical • P1 data • Metastases
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    MUC16 (Mucin 16, Cell Surface Associated)
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    zelenirstat (PCLX-001)
    2years
    Phase I Trial of PCLX-001 in B-cell Non-Hodgkin Lymphoma and Advanced Solid Malignancies (clinicaltrials.gov)
    P1, N=60, Recruiting, Pacylex Pharmaceuticals | Trial completion date: Jul 2024 --> Oct 2024 | Trial primary completion date: Jun 2023 --> Feb 2024
    Trial completion date • Trial primary completion date • Metastases
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    CD20 (Membrane Spanning 4-Domains A1)
    |
    CD20 expression
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    zelenirstat (PCLX-001)
    over2years
    Identification of a gene signature for cancers sensitive to N-Myristoylation inhibition (EACR 2023)
    By inhibiting this essential protein modification process, PCLX-001 shows high therapeutic potential in multiple cancer cell lines and animal models...The PCLX sensitivity score–91 (PSS-91) is higher in sensitive tumors compared to their associated normal tissue, in hematological cancers and in highly metabolically active tumors.ConclusionPCLX-001 is a drug that preferentially targets select tumor types in a manner reminiscent of synthetic lethality. In-depth analysis of sensitive cells allowed us to develop a PSS-91 sensitivity signature that will help identify future cancer indications and patients that would benefit from N-myristoyltransferase inhibitor therapy.
    Gene Signature
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    zelenirstat (PCLX-001)
    over2years
    Phase I Trial of PCLX-001 in B-cell Non-Hodgkin Lymphoma and Advanced Solid Malignancies (clinicaltrials.gov)
    P1, N=60, Recruiting, Pacylex Pharmaceuticals | Trial completion date: Jul 2023 --> Jul 2024 | Trial primary completion date: Feb 2023 --> Jun 2023
    Trial completion date • Trial primary completion date • Metastases
    |
    CD20 (Membrane Spanning 4-Domains A1)
    |
    CD20 expression
    |
    zelenirstat (PCLX-001)