GlycoMimetics has designed and synthesized a family of compounds that target both E-Selectin and CXCR4; the lead compound is GMI-1359. CXCR4 has been successfully targeted by the approved drug plerixaflor, which is marketed by Sanofi as Mozobil. Mozobil has been approved for use to improve stem cell mobilization for transplant and is in clinical trials for use in combination with chemotherapy in hematological malignancies (types of cancer that affect blood, bone marrow, and lymph nodes). Thus, targeting CXCR4 has demonstrated clinical benefit in certain settings.
Data in the scientific literature and from GlycoMimetics’ pre-clinical studies suggest that targeting both E-selectin and CXCR4 could provide enhanced benefits.
- Data presented at the December 2011 American Society of Hematology (ASH) meeting showed in a model of acute myeloid leukemia (AML) that molecules from this compound family, combined with chemotherapy, enhanced clearance of blast cells from the bone marrow, compared to chemotherapy alone.
- Two posters presented at the AACR Annual Meeting 2015 summarized research data on GMI-1359, demonstrating its anti-tumor activity both alone and in combination with chemotherapy in preclinical models of pancreatic and prostate tumor growth.
- An oral presentation and a poster shared at the AACR Annual Meeting 2016 highlighted data on GMI-1359, demonstrating anti-tumor activity in preclinical models of pancreatic cancer and AML, respectively. In a pancreatic cancer model, GMI-1359 showed significant disruption of the tumor microenvironment and inhibited tumor metastasis. In an AML model, while either GMI-1359 or sorafenib alone reduced tumor burden, antitumor activity was significantly enhanced when GMI-1359 was given in combination with sorafenib, over either treatment alone.
We are exploring use of compounds in this family in preclinical models of a variety of cancers, particularly those prone to metastasis to the bone.
Combining E-Selectin and CXCR4 targeting in a single molecule may provide next-generation, first-in-class opportunities following on the success of Mozobil and other CXCR4 antagonists, particularly for treatment of certain blood cancers and cancers involving metastasis to bone. In a paper published in Science Translational Medicine in May 2016, researchers at Duke University—together with GlycoMimetics scientists—demonstrated the key roles of both E-selectin and CXCR4 in trafficking of breast cancer cells to bone marrow.
GMI-1359 has not approved for use by any health authority anywhere in the world.
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