AU4-53 / Aucentra - LARVOL DELTA

Evaluation of two novel Cyclin Dependent Kinase 9 inhibitors for the treatment of Myeloid Cell Leukaemia 1 (MCL1) high Chronic Lymphocytic Leukaemia (IWCLL 2025) - "The CDK9 inhibitor VIP152 has been shown to significantly reduce disease burden and improve overall survival in a murine CLL model (Sher et al, 2022), providing a rationale for the use of CDK9 inhibitors in CLL.We evaluated two novel selective CDK9 inhibitors, AU4-53 and AU11-8, for the treatment of CLL and hypothesised that patients with high MCL1 expression will be particularly responsive and that patients with high BCL2 and MCL1 expression may benefit from combination therapy with venetoclax. Peripheral blood expression of BCL2, BCL-XL and MCL1 was measured in primary CLL cells by multi-colour flow cytometry. The novel selective CDK9 inhibitors AU4-53 and AU11-8 show in vitro efficacy in CLL, implicating targeted inhibition of this kinase as an exciting therapeutic strategy for the treatment of MCL1 high CLL."

IO biomarker • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • ANXA5 • BCL2L1 • CD40LG • CDK9 • MCL1 • TLR9