GMI-1070 is a synthetic glycomimetic molecule, which was rationally designed to inhibit all three selectin types (a pan-selectin inhibitor). Selectins are glycoprotein cell adhesion molecules implicated in inflammatory processes.  As inhibition of all three selectin types (E-selectin, L-selectin and P-selectin) may be required for adequate therapeutic activity in certain inflammatory disorders, we believe that our compound’s ability to inhibit all selectins will provide distinct advantages over other approaches that target only one selectin, or which are so broadly active as to be non-specific .

GlycoMimetics has selected vaso-occlusive crisis of sickle cell disease as the first indication to explore with GMI-1070. Inflammation is a key mediator of vaso-occlusive crisis, a condition which represents a significant unmet medical need.  Sickle cell disease is one of the most prevalent genetic disorders in the US, affecting over 80,000 people.  It is a chronic condition with substantial morbidity and mortality, responsible for more than 75,000 hospitalizations per year in the US with an average stay of approximately 6 days. In March of 2009, GMI-1070 was awarded Orphan Drug status for vaso-occlusive crisis by the FDA. 

The main clinical feature of sickle cell disease is periodic painful vaso-occlusive episodes, known as vaso-occlusive crises or pain crises, which result in significant clinical complications.   Treatment for vaso-occlusive crisis consists primarily of supportive therapy, in the form of hydration and pain control, typically requiring extended hospitalization. No other therapies have been effective in aborting a vaso-occlusive crisis once it has begun. GMI-1070 is intended to treat vaso-occlusive crisis by inhibiting the enhanced cell adhesion which causes the ischemia and pain.

In March 2009, GlycoMimetics, Inc. announced the successful completeion of Phase I clinical trials of GMI-1070 to evaluate the compound’s safety and pharmacokinetics.  Preclinical studies in a sickle cell mouse model demonstrate significant promise for GMI-1070 in the treatment of vaso-occlusive crisis. Results of studies of GMI-1070 in other animal models include normalized blood flow, reduced inflammation and increased survival.

We believe that GMI-1070 may have a number of potential applications, including hematologic cancers in which selectins may play a significant role. Selectin-mediated cell adhesion may result in chemotherapy resistance. Selectins have also been shown to facilitate dissemination of cancer cells to bone marrow.  Initial evidence from preclinical blood cancer studies suggests that GMI-1070 may prevent selectin-mediated cancer cell adhesion.  GlycoMimetics is currently evaluating the potential to utilize GMI-1070 in combination with chemotherapy.