AB Science Identifies AB8939 as a Drug Candidate for Refractory Acute Myeloid Leukemia
AB Science announces the publication of a preclinical study on bioRxiv regarding AB8939, a new synthetic molecule developed to treat refractory acute myeloid leukemia. This molecule is currently undergoing a Phase I/II clinical trial, according to the company's statement.
Dual Mechanism of Action
AB8939 combines two distinct modes of action, the company states. On one hand, the molecule destabilizes microtubules by binding to the colchicine site on beta-tubulin, causing cell cycle arrest and apoptosis of proliferating tumor cells. On the other hand, it inhibits aldehyde dehydrogenases ALDH1 and ALDH2, enzymes that are overexpressed in tumors and associated with cancer stem cells as well as resistance to treatments. According to AB Science, this dual approach targets both active cancer cells and quiescent resistant stem cells.
Preclinical Efficacy Demonstrated
The published preclinical studies show that AB8939 exhibits antiproliferative activity with nanomolar IC50 values against various human cancer cell lines, particularly in hematopoietic cancers, according to the group. The molecule maintains its effectiveness against cells resistant to conventional chemotherapy, notably those overexpressing P-glycoprotein or beta 3-tubulin. In murine models and patient-derived xenografts of high-risk acute myeloid leukemia, including cases with MECOM rearrangement and TP53 mutations, AB8939 significantly inhibited tumor growth and increased survival rates. Combination with azacitidine led to an almost complete elimination of the disease in these experimental models.
Ongoing Clinical Trial Phase I/II
AB8939 is currently being evaluated in the Phase I/II clinical trial AB18001 in patients with recurrent or refractory acute myeloid leukemia. The first two stages recruited 28 and 13 patients respectively and established the maximum tolerated dose at 21.3 mg per square meter after 3 and 14 consecutive days of treatment. The group recently received regulatory approval to initiate the third stage evaluating the combination of AB8939 with venetoclax. The material composition of AB8939 is protected by patents issued until 2026 in major geographical areas, including Europe, the United States, China, and Japan. An additional patent application for a specific medical use could extend this protection until 2044 for certain patient subpopulations. The molecule has also received orphan drug designation from the EMA and FDA, granting commercial exclusivity for 10 years in Europe and 7 years in the United States from the product's registration.
