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    DRUG:

    YF2

    i
    Other names: YF2, YF-2
    Company:
    Columbia University Irving Medical Center, Ichor Life Sci
    Drug class:
    Histone acetyltransferase activator
    7ms
    Combination Epigenetic Therapy Using YF2, a First-in-Class Histone Acetyltransferase Activator, Restores Immunogenicity in Diffuse Large B-Cell Lymphoma (ASH 2023)
    Other epigenetic therapies, such as tazemetostat and belinostat, are approved for use in follicular and T-cell lymphoma, respectively, but have limited single agent activity in DLBCL. In summary, these data propose YF2 combination epigenetic therapy as a means to increase immunogenicity in CBP/p300- and EZH2-mutated DLBCL. While our preliminary mouse experiment provided promising initial results, an expanded study is underway to statistically confirm the exciting trends that we observed.
    Epigenetic controller
    |
    CD8 (cluster of differentiation 8) • B2M (Beta-2-microglobulin) • CREBBP (CREB binding protein) • CD4 (CD4 Molecule)
    |
    EZH2 mutation • CREBBP mutation • EZH2 wild-type
    |
    Tazverik (tazemetostat) • YF2 • Beleodaq (belinostat)
    7ms
    First-in-Class HAT Activator (YF2) Combined with JAK/STAT Inhibitor (ruxolitinib) Unveils Potential Novel Treatment Approach for HDAC Inhibitor-Resistant CTCL (ASH 2023)
    In addition, we generated a belinostat-resistant H9 cell line (H9-belino-R) by incrementally exposing H9 to increasing concentrations of belinostat...H9-belino-R retained significant resistance to other HDAC inhibitors such as romidepsin [(H9: IC50 = 0.97nM (SEM ± 0.030), H9-belino-R: IC50 = 1.38nM (SEM ± 0.028)] and panobinostat [H9: IC50 = 3.11nM (SEM ± 0.19), H9-belino-R: IC50 = 9.00nM (SEM ± 1.55)] as measured by the CellTiter-Glo Viability Assay...These preliminary findings provide us with evidence that suggests that the combination of YF2 and ruxolitinib can serve as a novel treatment combination for CTCL. Further study is planned to explore this treatment in murine models of disease.
    IO biomarker
    |
    BCL2 (B-cell CLL/lymphoma 2) • BCL2L1 (BCL2-like 1) • JAK1 (Janus Kinase 1) • ANXA5 (Annexin A5) • BAK1 (BCL2 Antagonist/Killer 1)
    |
    JAK1 mutation
    |
    Jakafi (ruxolitinib) • Farydak (panobinostat) • Istodax (romidepsin) • YF2 • Beleodaq (belinostat)
    over1year
    First-in-Class Histone Acetyltransferase (HAT) Activator, YF2, Modulates Immune Evasion in DLBCL, Enhancing the Effects of Immune Checkpoint Blockade (ASH 2022)
    Based on the success of YF2 in the preclinical setting, the use of this first-in-class drug for treatment of lymphoma was approved to proceed in clinical studies in patients with relapsed/refractory lymphoma. Patient samples will be collected and analyzed for immune response.
    Checkpoint inhibition • PD(L)-1 Biomarker • IO biomarker • Epigenetic controller
    |
    CD8 (cluster of differentiation 8) • BCL6 (B-cell CLL/lymphoma 6) • LAG3 (Lymphocyte Activating 3) • CREBBP (CREB binding protein) • TIGIT (T Cell Immunoreceptor With Ig And ITIM Domains 2) • CD4 (CD4 Molecule) • EP300 (E1A binding protein p300) • HDAC3 (Histone Deacetylase 3)
    |
    PD-L1 expression • PD-1 expression • MHC-II expression • BCL6 overexpression • PD-L1-L
    |
    YF2
    over2years
    Histone Acetyltransferase (HAT) Activator, YF2, Modulates the p53:BCL6 Axis and Antigen Presentation in Diffuse Large B-Cell Lymphomas (ASH 2021)
    We first developed cell lines to be 10-fold resistant to HDACi romidepsin. Additionally, YF2 treatment modulates the p53:BCL6 axis, cell cycle progression, and antigen presentation pathway potentially restoring immune surveillance. These results support future clinical application of YF2 in HAT mutated lymphomas.
    Epigenetic controller
    |
    CCND1 (Cyclin D1) • BCL6 (B-cell CLL/lymphoma 6) • IFNG (Interferon, gamma) • CREBBP (CREB binding protein) • EP300 (E1A binding protein p300) • CDKN1A (Cyclin-dependent kinase inhibitor 1A)
    |
    TP53 mutation • CCND1 expression • EP300 mutation
    |
    Istodax (romidepsin) • YF2