Katy Rezvani received this year’s E. Donnall Thomas Prize for her work on natural killer (NK) cells at the annual meeting of the American Society of Hematology (ASH). It was not love at first sight, though.
Disrupting apoptosis is a mechanism that cancerous cells use to avoid being killed; this can be performed by overexpressing pro-survival factors, such as induced myeloid leukemia cell differentiation protein Mcl-1. Researchers from Abbvie Inc. have recently published preclinical data on a potent and selective Mcl-1 inhibitor, ABBV-467, for the treatment of hematologic cancers.
In work conducted at China Pharmaceutical University, synthesis and optimization of a new series of cyclin-dependent kinase 9 (CDK9) inhibitors bearing a flavonoid scaffold led to the identification of compound [I] as the lead candidate, with IC50 of 6.7 nM for CDK9 and >80-fold selectivity over CDK2 and most other CDK family members.
Researchers from Exscientia plc presented preclinical data for the novel reversible LSD1 inhibitor EXS-74539, being developed as a monotherapy or in combination with standard of care for the treatment of oncology and hematology indications including acute myeloid leukemia (AML) and small-cell lung cancer.
Caribou Biosciences Inc. has received FDA clearance of its IND application for CB-012, an allogeneic anti-C-type lectin-like molecule-1 (anti-CLL-1) chimeric antigen receptor (CAR) T-cell therapy. CLL-1 is highly expressed on acute myeloid leukemia (AML) cells and leukemic stem cells, but it is not expressed on hematopoietic stem cells.
Recurrent driver mutations in FMS-related receptor tyrosine kinase 3 (FLT3) occur in around one-third of patients with de novo acute myeloid leukemia (AML). Although most FLT3 mutations are secondary events in leukemogenesis, they are associated with accelerated clonal expansion and disease progression, and treatment with the tyrosine kinase inhibitor midostaurin has been shown to increase patients’ long-term survival. However, the efficacy of FLT3 inhibitors in eliminating FLT3-mutated clones is variable.
Finding suitable antigens for immunotherapy of myeloid malignancies, particularly acute myeloid leukemia (AML), is an urgent clinical need. Most AML candidate targets, including CD123, are co-expressed by hematopoietic stem and progenitor cells (HSCPs), with the subsequent risk of myelosuppression associated with myeloid cell-targeted chimeric antigen receptor (CAR) T therapy.
Syndax Pharmaceuticals Inc. is gearing up for a U.S. FDA filing by the end of 2023 on the back of positive data from a pivotal phase I/II study testing menin inhibitor revumenib in adult and pediatric patients with relapsed/refractory KMT2A-rearranged acute myeloid leukemia and acute lymphoid leukemia.
.png?height=488&t=1670008838&width=650 "Acute myeloid leukemia")