Advanced BioDesign

Lyon (France), October 29, 2024 – Acute Myeloid Leukemia (AML) remains a major medical challenge despite recent advances in targeted molecular therapies. A recent study published in the Journal of Cellular Molecular Medicine1) has highlighted a crucial aspect of leukemic cell resistance to chemotherapy: their increased ability to manage cellular stress and produce reactive oxygen species (ROS), thanks to high activity of the ALDH1A1/2 enzymes. The results show that ROS levels and ALDH1A1/2 activity in the bone marrow of AML patients are correlated with the ELN 2022 prognostic groups and overall survival. Patients with high ROS levels have a significantly lower median overall survival (8.2 months) compared to those with low ROS levels (24.6 months).
After the first line of treatment, a significant increase in ROS levels and ALDH1A1/2 activity was observed, particularly in refractory patients. These findings underpin the development of ABD-3001, a competitive and irreversible inhibitor of ALDH1. In vitro tests showed that ABD-3001 can inhibit the proliferation of patient-derived leukemic cells by disrupting the redox balance.

Geoffroy Venton, MD of APHM & first author, states: “Our research shows that inhibiting ALDH1A1/2 enzymes can play a crucial role in combating leukemic cell resistance to chemotherapy. ABD-3001 has shown promising results in the laboratory, and we are eager to see its efficacy confirmed in clinical trials.”

ABD-3001 is currently being evaluated in the first multicenter phase 1 clinical trial, named “ODYSSEY” (NCT05601726), for patients with relapsed AML. The initial safety results are eagerly awaited by the medical community.

Ismail CEYLAN, CEO at Advanced BioDesign, adds: “It is the result of exceptional scientific and operational work by our teams. The launch of the ODYSSEY clinical trial marks an important milestone for our company. Result gathered in the first part show us the tolerability of our approach and beyond our expectation with a compassionate use treatment allowed by French authorities for one patient. We hope that ABD-3001 can offer a new therapeutic option for patients with relapsed AML.”

About the Study: The study was conducted by a team of researchers specializing in oncology and hematology, with support from several international research centers. The full results will be presented at the next annual congress of The European Hematology Association.

Reactive oxygen species and aldehyde dehydrogenase 1A as prognosis and theragnostic biomarker in acute leukaemia patients