AB8939 is a next generation, synthetic microtubule destabilizer.
AB8939 key differentiating factors

Compound AB8939 is a structurally novel, small chemical molecule, synthesized tubulin inhibitor that can circumvent P-glycoprotein (Pgp) and myeloperoxidase (MPO) mediated resistance, thereby conferring an important advantage over traditional tubulin inhibitors.

AB8939 is initially being developed in acute myeloid leukemia (AML) because cancer cells proliferate rapidly in this disease. In HL-60 and U-937 cell lines, AB8939 inhibits proliferation with an IC50 of approximately 5 nM, compared with more than 1,000 nM for doxorubicin. This insensitivity to myeloperoxidase is an advantage over vinca alkaloids (vincristine or vinblastine).

The aim of AB Science with compound AB8939 has been to design an ultra-selective small-molecule drug, having strong antiproliferative properties and an acceptable safety profile with minimal cardiac or neuronal toxicity.

AB8939 preclinical data

The therapeutic potential of AB8939 in AML was demonstrated using cytarabine (Ara-C) resistant and azacitidine resistant patient-derived xenograft (PDX) models4. Ara-C is considered the clinically most relevant cytotoxic agent for AML treatment, while azacitidine is a widely used hypomethylating agent for AML1, 2, 3.

AB8939 substantially decreased the concentration of blasts in blood (38d post-graft), bone marrow (BM) and spleen (52d post-graft) relative to azacitidine (Vidaza®)4.

The therapeutic potential of AB8939 in AML was demonstrated in vivo using an Ara-C resistant PDX model. Single agent AB8939 substantially decreased the concentration of blasts in blood and bone marrow, and decreased tumor growth relative to Ara-C.

Clinical development

AB8939 is being evaluated in the Phase 1/2 study AB18001 (NCT05211570), which has been open since June 2022, in patients with relapsed or refractory acute myeloid leukaemia. The first three stages of Phase 1 have been completed; stage 3, evaluating AB8939 in combination with venetoclax, was reported in June 2026. AB8939 received orphan drug designation in acute myeloid leukaemia from the Food and Drug Administration on 7 November 2019 and from the European Medicines Agency on 23 April 2025.

References

  1. Humbert M, et al. Anticancer Activity of a Highly Potent Small Molecule Tubulin Polymerization Inhibitor, AB8939. Blood. 2019;134(Supplement 1):2075. doi:10.1182/blood-2019-122540
  2. Goubard A, et al. In Vivo Assessment of the Next Generation Microtubule-Destabilizing Agent AB8939 in Patient-Derived Xenograft Models of Acute Myeloid Leukemia. Blood. 2019;134(Supplement 1):5142. doi:10.1182/blood-2019-127143
  3. Goubard A, et al. AB8939, a Microtubule-Destabilizing Agent with Potential to Overcome Multidrug Resistance, Is Active across the Range (M0-M7) of Acute Myeloid Leukemia Subtypes. Blood. 2019;134(Supplement 1):5154. doi:10.1182/blood-2019-127021
  4. Humbert M, Letard S, Goubard A, et al. Identification of AB8939, a novel synthetic microtubule destabilizer and ALDH inhibitor that overcomes multidrug resistance in tumor cells as a drug candidate for the treatment of refractory acute myeloid leukemia. bioRxiv. 2025. Preprint. doi:10.64898/2025.12.10.692519.