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    DRUG:

    BTM-3566

    i
    Other names: BTM-3566
    Company:
    Bantam Pharma
    Drug class:
    EIF-2 kinase modulator
    1year
    Targeting aggressive B-cell lymphomas through pharmacological activation of the mitochondrial protease OMA1. (PubMed, Mol Cancer Ther)
    Once-daily oral dosing of BTM-3566 resulted in complete regression of xenografted human DLBCL SU-DHL-10 cells and complete regression in 6 of 9 DLBCL patient-derived xenografts. BTM-3566 represents a first- of-its kind approach of selectively hyperactivating the mitochondrial ISR for treating DLBCL.
    Journal
    |
    ATF4 (Activating Transcription Factor 4)
    |
    BTM-3566
    over1year
    Pharmacokinetics and pharmacodynamics of the novel OMA1 activator BTM 3566 in a mouse model of diffuse large B-cell lymphoma (AACR 2023)
    The data support the use of both ATF4 transcripts and OPA1 cleavage as robust PD markers of target engagement and pathway effect in human clinical trials. An Investigational New Drug application for BTM3566 in B-cell malignancies has been approved with initiation of first in human clinical trials planned for spring 2023.
    PK/PD data • Preclinical
    |
    MCL1 (Myeloid cell leukemia 1) • ATF4 (Activating Transcription Factor 4) • CDKN1A (Cyclin-dependent kinase inhibitor 1A) • DDIT3 (DNA-damage-inducible transcript 3) • TRIB3 (Tribbles Pseudokinase 3)
    |
    BTM-3566
    over2years
    BTM-3566, A NOVEL ACTIVATOR OF THE MITOCHONDRIAL STRESS RESPONSE ERADICATES DIFFUSE LARGE B-CELL LYMPHOMA IN MICE (EHA 2022)
    Conclusion We describe a novel antitumor mechanism in DLBCL, where BTM-3566 induces mitochondrial stress, activating the OMA1-DELE1-HRI-eIF2a-ATF4 pathway leading to apoptosis and tumor regression. An IND application in DLBCL has been completed with initiation of first in human clinical trials planned in 2022.
    Preclinical • IO biomarker
    |
    ATF4 (Activating Transcription Factor 4) • EIF2A (Eukaryotic Translation Initiation Factor 2A) • EIF2S1 (Eukaryotic Translation Initiation Factor 2 Subunit Alpha)
    |
    BTM-3566
    over2years
    BTM-3655 co-opts mitochondrial quality control pathways to induce apoptosis, and complete tumor regression in DLBCL cell lines, xenografts and PDX models (AACR 2022)
    Taken together, these data support a novel antitumor mechanism in DLBCL, where BTM3566 induces mitochondrial stress, activating the OMA1-DELE1-HRI-eIF2a-ATF4 pathway leading to apoptosis and tumor regression. An Investigational New Drug application for BTM3566 in B-cell malignancies will be submitted by early Q1 2022 with initiation of first in human clinical trials the first half of 2022.
    Preclinical
    |
    ATF4 (Activating Transcription Factor 4) • EIF2A (Eukaryotic Translation Initiation Factor 2A) • EIF2S1 (Eukaryotic Translation Initiation Factor 2 Subunit Alpha)
    |
    BTM-3566
    3years
    Btm-3566, a Novel Activator of the Mitochondrial Stress Response Promotes Robust Therapeutic Responses in Vitro and In Vivo in Diffuse Large B-Cell Lymphoma (ASH 2021)
    In summary, we describe here a novel, highly potent activator of the mitochondrial ISR, which is well tolerated in mice and dogs, has favorable pharmacokinetics and induces robust DLBCL regression in-vivo. An IND application in B-cell malignancies will be completed by early Q1 2022 with initiation of first in human clinical trials the first half of 2022.
    Preclinical • IO biomarker
    |
    BCL2 (B-cell CLL/lymphoma 2) • MYD88 (MYD88 Innate Immune Signal Transduction Adaptor) • ATF4 (Activating Transcription Factor 4)
    |
    MYD88 mutation • MYC rearrangement • BCL2 rearrangement
    |
    BTM-3566