AB Science announces a new publication on biorxiv that identifies AB8939 as a promising drug candidate for treating refractory acute myeloid leukemia and potentially other cancers

Core Viewpoint - AB Science has published a new article identifying AB8939 as a promising drug candidate for treating refractory acute myeloid leukemia (AML) and potentially other cancers, highlighting its dual mechanism of action and effectiveness against multidrug resistance [1][2]. Group 1: Drug Candidate Characteristics - AB8939 is characterized as a novel synthetic microtubule destabilizer and ALDH inhibitor, showing potential for treating high-risk AML, particularly in cases with complex karyotypes, MECOM rearrangements, and TP53 mutations [3][4]. - The drug exhibits dual action against proliferating tumor cells through tubulin disruption and quiescent, resistant stem cells via ALDH inhibition, making it a unique therapeutic agent [3][4]. Group 2: Mechanism of Action - AB8939 acts as a microtubule-targeting agent by binding to the colchicine-binding site on β-tubulin, disrupting the microtubule network, leading to cell cycle arrest in the G2/M phase and subsequent apoptosis [4]. - It is a potent inhibitor of ALDH1 and ALDH2 enzymes, which are often overexpressed in tumors and associated with cancer stem cells, tumor progression, and resistance to therapy [4]. Group 3: Efficacy and Resistance - AB8939 demonstrates strong antiproliferative activity against various human cancer cell lines, particularly hematopoietic cancers, with IC₅₀ values in the nanomolar range [4]. - The drug can overcome major mechanisms of drug resistance, including P-glycoprotein (P-gp) efflux and high β3-tubulin expression, retaining efficacy in resistant AML patient blasts [4][5]. Group 4: Clinical Trials - AB8939 is currently being evaluated in a Phase I/II clinical trial (AB18001) for patients with refractory and relapsed AML, with regulatory approval received to initiate the third stage of the study [5][6]. - The first two stages of the trial involved 28 and 13 patients, respectively, determining the maximum tolerated dose (MTD) of 21.3 mg/m² after both three and fourteen consecutive days of treatment [6]. Group 5: Intellectual Property and Regulatory Status - AB8939 is protected by intellectual property rights until 2036 or even 2044, with a patent covering its composition and use in AML treatment granted in multiple countries [7][8][9]. - The drug has received orphan drug designation from both the European Medicines Agency (EMA) and the US Food and Drug Administration (FDA), granting it marketing exclusivity for 10 years in Europe and 7 years in the US [10].