YF2 / Ichor Life Sci, Columbia University Irving Medical Center - LARVOL DELTA

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 • Cutaneous T-cell Lymphoma • Hematological Malignancies • Lymphoma • Oncology • T Cell Non-Hodgkin Lymphoma • ANXA5 • BAK1 • BCL2 • BCL2L1 • JAK1

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 • B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Gene Therapies • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • T Cell Non-Hodgkin Lymphoma • B2M • CD4 • CD8 • CREBBP

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 • Epigenetic controller • IO biomarker • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Immune Modulation • Inflammation • Lymphoma • Oncology • BCL6 • CD4 • CD8 • CREBBP • EP300 • HDAC3 • LAG3 • TIGIT

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 • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • BCL6 • CCND1 • CDKN1A • CREBBP • EP300 • IFNG