Core Viewpoint - AB Science has announced the identification and characterization of a novel small synthetic molecule, AB8939, as a promising drug candidate for treating refractory acute myeloid leukemia (AML) and potentially other cancers [1] Group 1: Drug Candidate Characteristics - AB8939 is identified as a powerful compound with a dual mechanism of action, disrupting microtubule formation and inhibiting ALDH enzymes, which are linked to therapy resistance and the survival of leukemic stem cells [2][3] - The drug shows potential for treating high-risk AML cases, particularly those with complex karyotypes, MECOM rearrangements, and TP53 mutations [3] - AB8939 has demonstrated strong antiproliferative activity against various human cancer cell lines, especially hematopoietic cancers, with IC₅₀ values in the nanomolar range [4] Group 2: Mechanism of Action - AB8939 acts as a microtubule destabilizer by binding to the colchicine-binding site on β-tubulin, leading to cell cycle arrest and apoptosis [4] - It also inhibits ALDH1 and ALDH2, which are often overexpressed in tumors and associated with cancer stem cells and therapy resistance [4] - The drug can overcome major mechanisms of drug resistance, such as P-glycoprotein (P-gp) efflux and high β3-tubulin expression, allowing it to remain effective in resistant cancer cells [4] Group 3: 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 4: Intellectual Property and Regulatory Status - AB Science retains full ownership of the intellectual property rights for AB8939, with protection extending until 2036 or even 2044 for specific uses [7][9] - The drug has received orphan drug designation from both the European Medicines Agency (EMA) and the US Food and Drug Administration (FDA), granting marketing exclusivity for 10 years in Europe and 7 years in the US [10] Group 5: Preclinical Evidence - In preclinical models, AB8939 has shown significant inhibition of tumor growth and increased survival rates in Ara-C-resistant AML mouse models [12] - The drug effectively eradicated leukemic stem cells in patient-derived xenograft models, suggesting its potential to reduce the risk of disease relapse [12]