GlycoMimetics poster shows GMI-1271 reverses drug resistance in multiple myeloma models

GlycoMimetics to initiate myeloma trial in mid-2016.

“The data on GMI-1271 show a promising pathway toward reducing resistance to chemotherapy and other drugs in multiple myeloma,” said Helen Thackray, Vice President and Chief Medical Officer of GlycoMimetics. “We’re encouraged by the potential to use a biomarker to identify a specific population of multiple myeloma patients who might benefit from this therapy, and we intend to initiate a clinical trial in Europe in mid-2016.”

The data in the poster describes a preclinical model mimicking a very high-risk patient population with multiple myeloma. This high-risk group is defined by expression of higher levels of the E-selectin ligand HECA-452 on multiple myeloma cells. HECA-452 expression is also shown to increase in patients as disease progresses. In the animal model reported in the poster, bortezomib did not demonstrate any benefit in the treatment of myeloma with high expression of HECA-452. When GMI-1271 was combined with bortezomib, however, this resistance to bortezomib was overcome, and animals showed improvements in survival compared to bortezomib alone. Resistance to bortezomib is seen in the clinic with shorter and shorter duration of remission as patients’ disease progresses. Improving the response to bortezomib could improve clinical outcomes for high risk and relapsed patients with myeloma.

GMI-1271 targets E-selectin, a cell adhesion molecule that aids in blood cancer cell resistance to chemotherapy. The drug candidate also is in a Phase 1/2 clinical study designed to evaluate its safety, pharmacokinetics (PK) and efficacy when used together with chemotherapy in patients with acute myeloid leukemia (AML).

The abstract (Abstract #1805), entitled “E-selectin Ligand Expression Increases with Progression of Myeloma and Induces Drug Resistance in a Murine Transplant Model, which is Overcome by the Glycomimetic E-Selectin Antagonist, GMI-1271,” is available at ASH’s website.