Daiichi Sankyo Initiates First-in-Human Phase 1/2 Trial of Potent and Selective Menin Inhibitor DS-1594 for Relapsed/Refractory Acute Leukemias

April 11, 2021 News /BioValleyBIOON/ -- Daiichi Sankyo recently announced the evaluation of DS-1594, a selective small-molecule menin inhibitor, for the treatment of relapsed/refractory acute myeloid leukemiaLeukemiaThe first-in-human Phase 1/2 study in acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) has administered the investigational therapy to the first patient. This study is being conducted by The University of Texas MD Anderson Cancer Center under an existing strategic research collaboration.

Inhibition of the menin protein is being investigated as a novel therapeutic approach for acute leukemia harboring MLL rearrangements (MLLr) or NPM1 mutations (NPM1m), two genetic alterations that drive cancer initiation and progression. MLLr occurs in approximately 5%–10% of patients with acute leukemia and is associated with aggressive disease, reduced treatment response, and poor prognosis. NPM1m is present in about 30% of patients with acute myeloid leukemia (AML). Currently, there are no drugs specifically approved for the treatment of MLLr- or NPM1m-associated leukemia, nor are there any approved menin inhibitors.

Daiichi Sankyo Alpha PortfolioTumorArnaud Lesegretain, Vice President and Head of Research and Development, stated, “Studies have shown that the menin protein bound to MLL plays a critical role in the development and progression of MLL-rearranged (MLLr) leukemia. Our scientists have designed DS-1594 to inhibit the menin-MLL interaction and disrupt intracellular activities associated with leukemogenesis. In collaboration with MD Anderson, we will evaluate DS-1594 as a potential therapeutic option for patients with acute myeloid leukemia (AML) who have exhausted standard treatment regimens.”

MLL (Mixed Lineage Leukemia) gene, also known as KMT2A, in maintaining hematopoiesisStem Cellsaspects are important and are known to undergo chromosomal translocations or epigeneticGeneticschanges, leading to the expression of MLL fusion proteins that ultimately drive the formation and growth of leukemia. Approximately 5%-10% of acute leukemia cases involve MLL rearrangements (MLLr), with a 5-year overall survival rate of approximately 35%.。

NPM1 (Nucleophosmin 1) gene mutations lead to abnormal expression of the NPM1 protein, which is involved in cellular proliferation and other functions. NPM1 mutations (NPM1m) are observed in approximately 30% of patients with acute myeloid leukemia (AML), with a 5-year overall survival rate of approximately 50%.

Menin is a scaffold protein that interacts with various other proteins to regulate gene expression and cell signaling. The interaction between menin and MLL proteins is critical for the leukemogenic activity in MLL-rearranged (MLLr) leukemia and has been reported to play a key role in the pathogenesis of NPM1-mutated (NPM1m) leukemia. Scientific evidence supports the inhibition of the menin-MLL interaction as a therapeutic approach for acute leukemia. Currently, there are no drugs specifically approved for MLLr or NPM1m leukemia, nor are there any approved menin inhibitors.

DS-1594 is a potent and selective small-molecule menin inhibitor that targets and disrupts the protein–protein interaction between menin and MLL, thereby inhibiting the growth and proliferation of leukemia cells. In preclinical studies, DS-1594 demonstrated selective inhibition of the growth of AML and ALL cells harboring MLL rearrangements (MLLr), and exhibited robust and durable anti-Tumoractivity and an acceptable safety profile. DS-1594 is an investigational drug that has not been approved for any indication in any country, and its safety and efficacy have not yet been established.(Bioon.com)

Original Source: Phase 1/2 Trial Initiated for Daiichi Sankyo’s Menin Inhibitor DS-1594 in Patients with Acute Myeloid Leukemia and Acute Lymphoblastic Leukemia