GlycoMimetics is developing uproleselan, a specific E-selectin inhibitor, to be used in combination with chemotherapy to treat patients with AML, MM and potentially other hematologic cancers.
E-selectin plays a critical role in binding cancer cells within vascular niches in the bone marrow, which prevents the cells from entering circulation where they can be more readily killed by chemotherapy. In separate animal studies, uproleselan mobilized AML and MM cancer cells out of the bone marrow, making them more sensitive to chemotherapy. In both the AML and MM studies, tumor burden was significantly reduced in the animals treated with a combination of chemotherapy and uproleselan as compared to animals treated with chemotherapy alone. In addition, the combination of uproleselan with chemotherapy resulted in improved survival rates for the treated animals, compared to chemotherapy alone. In other animal studies, uproleselan appeared to also protect normal cells from some of the side effects of chemotherapy. Common side effects of chemotherapy include bone marrow toxicity resulting in neutropenia, which is an abnormally low number of neutrophils, the white blood cells that serve as the primary defense against infection, and mucositis, which is the inflammation and sloughing of the mucous membranes lining the digestive tract. Animals treated with uproleselan and chemotherapy had less severe neutropenia and mucositis and lower bone marrow toxicity as compared to animals treated with chemotherapy alone. We believe that treatment with uproleselan may result in lower bone marrow toxicity due to its inhibition of E-selectin, which inhibition makes stem cells in the bone marrow divide less frequently, thereby protecting them from chemotherapy agents that target rapidly dividing cells.
In 2017 we completed enrollment and in December 2017, at the annual meeting of the American Society of Hematology, we presented clinical data from our recently completed Phase 1/2 clinical trial in defined populations of patients with AML that showed high remission rates, improved overall survival and improved duration of survival, as compared to historical controls. In addition, the data suggested a favorable safety, pharmacokinetic, or PK, and biomarker profile for uproleselan. Full details regarding the Phase 1/2 results presented at ASH 2017 may be found here: DeAngelo-GMI-1271-201-ASH-2017-Abstract-894.pdf
We have also initiated a Phase 1 multiple ascending dose-escalation trial of uproleselan in defined populations of patients with MM and plan to continue enrollment of the trial in 2018. We anticipate initial topline data during 2019 in this trial.
The FDA has granted Breakthrough Therapy Designation for uproleselan in adults with relapsed or refractory AML. Additionally, uproleselan has received Fast Track designation from the FDA, which may lead to speedier delivery to people living with AML if the treatment is found to be effective. The European Union granted Orphan Drug Designation for uproleselan in AML, a designation the FDA granted the drug candidate in 2015. Uproleselan has not been approved for use by any worldwide health authority.
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