Microtubules
The internal scaffold organises division of the leukaemia cell.
Medicine in development
AB8939
Acute myeloid leukaemia (AML)
A synthetic molecule designed to directly target cancer cells.
Overview
A second molecule with a distinct development path
AB8939 is the second molecule developed by AB Science, alongside masitinib. The two follow very different paths. Masitinib acts on cells of the immune system, while AB8939 directly targets cancer cells.
It is a fully synthetic molecule designed and patented by AB Science, which owns all rights to it. Its priority indication is acute myeloid leukaemia, a blood cancer in which abnormal cells multiply rapidly in the bone marrow, spread into the bloodstream and prevent the normal production of blood cells. Patients who cannot receive intensive chemotherapy currently have few effective treatment options.
AB8939 was selected for this disease because leukaemia cells divide very rapidly, making them particularly sensitive to its mechanism of action. The molecule is currently being evaluated in a Phase 1/2 study, alone or in combination with an existing treatment. This is study AB18001 (NCT05211570).
Mechanism of action
Targeting two key mechanisms of the disease
Two obstacles explain why acute myeloid leukaemia so often returns after treatment. The first is resistance: cancer cells manage to neutralise medicines, particularly by expelling them from the cell before they can act. The second is the persistence of leukaemia stem cells, dormant cells that treatments do not reach effectively and that can restart the disease. AB8939 was designed to address both problems at the same time.
Action of AB8939
The molecule targets and destabilises the microtubules required for cell division.
Breakdown of the scaffold
The structure becomes disorganised and the cell can no longer complete division.
Cell collapse
Cell division is blocked and the leukaemia cell collapses.
Mechanism 1
Resistance
AB8939 is not expelled by the efflux pump and is not degraded by myeloperoxidase. It therefore bypasses two common mechanisms that neutralise medicines.
Mechanism 2
Persistence
AB8939 blocks the ALDH1A1 and ALDH2 enzymes on which leukaemia stem cells depend. It could therefore reach the reservoir of cells capable of surviving treatment and restarting the disease.
Development phasePhase 1/2
Protocol duration14/28 days
Target population≈ 80,000 patients — Europe and United States(patients not receiving a stem cell transplant and relapsing after first-line treatment)
Market size€600 million — Europe + United States