Myelodysplastic syndromes (MDS) are estimated to occur at a rate between 4 and 5 for every 100,000 people in the world. Approximately 13,000 people in the United States and 2,500 in France are diagnosed each year.
40% of MDS patients have an innate resistance to azacitidine, the standard treatment for severe MDS, and even 100% become resistant during treatment. 33% of MDS evolve in acute myeloid leukemia (AML). The median survival of patients with AML is 4 months.
HOW IT WORKS
A scientific team demonstrated that two new classes of triazole derivatives:
The clinical positioning of these triazole derivatives should be on MDS patients resistant to azacitidine and/or evolving into AML.
KEY BENEFITS vs. STATE OF THE ART
Reference MDS treatments are azacitidine (Vidaza®), decitabine (Dacogen®), lenalidomide (Revlimid®) and imatinib (Gleevec®) but new therapeutic options are always required:
In vitro results: molecules of this family demonstrated in vitro submicromolar IC50 (200-900nM) on various MDS and AML cell lines,
In vivo results: other molecules of this family demonstrated in vivo activities (5-10 mg/kg, i.p.) in various mouse models of cancer (MDS, AML, CML...),
Ongoing lead optimization, and preclinical validation on MDS/AML mouse models.
Myelodysplastic syndromes with resistance to azacitidine
Myelodysplastic syndromes evolving into acute myeloid leukemia
Acute myeloid leukemia and Chronic myeloid leukemia